Although the ancient Greeks and Romans recognized the idea of authorship and personal property, the modern concept of patents began in 15th century Europe. Due to changes during that period, such as economic protection, competition, and the dissemination of ideas with the invention of the printing press, the concept of patenting began to take shape.
Now, six hundred-or-so-years later, patenting is continuing to take shape, at least as far as gene patenting is concerned. It was only in 1980 that the U.S. Supreme Court held that researchers could patent living material, stating that “anything under the sun that is made by the hand of man” is patentable. In this case, the material was a bacterium genetically engineered to degrade crude oil, invented by Ananda Chakrabarty. However, the United States Patent and Trademark Office (USPTO) subsequent interpretation of the Supreme Court’s conclusion, especially in the area of gene patenting, has led to debate and calls to change the system. Some of the questions raised are moral and some economic. Most of all, the questions revolve around what should be patentable and who should be protected by patent law.
History and Background of Patents
The United States government’s official patent granting office is the United States Patent and Trademark Office (USPTO). Patents, according to the USPTO, protect inventors and investors, and promote technological advancements in the United States. Over 6 million patents have been issued by the U.S. government since the first patent in 1790, and in 2001 alone, USPTO issued 182,223 patents.
When the U.S. Constitution outlined the duties of the congress, it gave Congress the power to provide protection to inventors in Article 1, Section 8, Clause 8, which reads, “The Congress shall have power. . . To promote the progress of science and useful arts, by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries.” This led to the establishment over time of the USPTO.
Today, the USPTO grants patents based on a specific set of criteria, which are outlined in the section called What Can be Patented. A patent is a property right granted by the United States government to an inventor “to exclude others from making, using, offering for sale, or selling the invention throughout the United States or importing the invention into the United States” for a limited time in exchange for public disclosure of the invention when the patent is granted.
What Can be Patented
The criteria to issue a patent requires that the invention is: 1. novel (or has never been known or used by anybody else anywhere in the world before it was filed); 2. nonobvious to one of ordinary skill in the relevant field of technology; and 3. useful, or, in other words, have at least one beneficial application.
Inventions usually fall into categories; a process, machine, article of manufacture, or composition of matter can be patented. However, naturally occurring organisms or phenomenon cannot be patented, nor can scientific theories, mathematical methods, or machines defying the laws of nature. These are considered ineligible subject matter for a patent. Thus, falling into the category of patentable subject matter is a fourth criterion for obtaining a patent on an invention.
The fifth requirement for obtaining a patent is providing a sufficient disclosure of the invention. Part of the bargain for obtaining a patent is the disclosure of how to make and use the invention. In other words, the inventor must guarantee that the public can practice the invention – and thus compete with the inventor – once the patent term expires. The disclosure requirements also put the invention into the public domain of knowledge, allowing others to rely on that information to create further developments, such as a way to avoid the inventor’s patent. The United States patent laws thus require a written description of the invention; a description of how to make and use the invention so as to enable one of ordinary skill in that field to practice the invention; and the inventor’s best mode of the invention, i.e. the best way of practicing the invention. All of these disclosure requirements must be satisfied in order for the patent to issue.
In most cases, a patent-holder gets 20 years of protection from the date the patent application is filed. Patent applications are published 18 months after the application is filed. This applies not only in the United States, but world-wide as part of the international Patent Cooperation Treaty. The Patent Cooperation Treaty allows an inventor to file one patent application and to thus receive the benefit of that filing date internationally to all countries listed on the application that are part of the Patent Cooperation Treaty. Preserving the date of application is important because it freezes the time frame by which the invention’s novelty and nonobviousness is assessed. In other words, later developments after the application date cannot be used against the inventor. The inventor must eventually apply for patents in all countries they seek protection in based on processes outlined in the treaty. The same goes conversely. Any inventor, regardless of his/her citizenship, may apply for a patent on the same basis as a U.S. citizen.
Research Exemptions and the Public Domain
All patent applications are released into the public domain either when the patent is granted or after eighteen months if prosecution of the patent in the USPTO take longer than eighteen months. The information is available for everyone to review, but if someone wishes to actually use the invention, he or she will have to receive the permission of the patent holder. The patent holder can require the user to pay royalties or licensing fees to use the invention, or the patent holder can completely deny a prospective user the right to use the invention altogether. Royalties and licensing are left up to the patent holders to decide how to arrange them. A license is a contract between a patent holder and a second party who wants to use invention. Royalties, arranged in a license agreement, involve paying a proportion of money made from the sale of products developed from patent information to the patent holder.
The only exemptions from having to make licensing arrangements are the research use doctrine and FDA research. As long as researchers are using the patented information to conduct research or experimentation and the user does not profit from the research, the researchers are not infringing on the patent. The research use doctrine has been interpreted very narrowly and researchers must be careful that they are engaged in purely academic research. The FDA research exception permits any kind of research to be conducted as long as the research is done to submit information to the FDA. The FDA research exception does not apply to biotechnology, however, including gene patents.
Background of Gene Patenting
In 1980, the U.S. Supreme Court ruled that scientists could patent living material, and since that time, over 2,000 patents have been issued for genetic material. However, naturally occurring organisms, phenomenon, or chemicals cannot be patented. In most cases of genetic material, the material must be isolated, purified, or modified in some way. “Gene patenting” can refer to the patenting of the process involved in isolating DNA (deoxyribonucleic acid) or the DNA itself purified from the human body by removing, for example, the “junk” DNA that does not act as part of the gene. The inventor must also explain what a possible use(s) for the gene there might be to receive a patent. A researcher cannot simply find something in the human body and receive a patent for it on the basis of its discovery alone. Moreover, a person cannot be patented nor can part of a person be patented-including their genes in their natural state. Patents mainly give companies the rights to use the gene for diagnostic tests and therapies developed from the research rather than to the gene itself.
Gene patenting extends to genes, gene fragments (also called express sequence tags or ESTs), single nucleotide polymorphisms (or SNPs), gene tests, proteins, and methods of treating genetic disorders. However, questions exist about at what point, from the discovery of a gene fragment to the development of a product, a patent should be rewarded. Below is a list of patentable gene products:
cDNA: Also called complimentary DNA. A cDNA molecule is a laboratory-made gene that only contains the part of the gene that is expressed. Only three to four percent of the vast quantity of DNA in the human genome is expressed. In the lab, copies of these natural DNA sequences are made, the non-functioning base sequences are removed, and the information-rich parts are spliced together, providing researchers a way to quickly get to the important areas of a gene.
Genes: Researchers patenting genes must first isolate the genes. Usually, they take a blood sample, and from that, they extract the DNA (the building blocks of genes). DNA does not exist in nature in isolation from an organism. DNA only exists in cells and its purpose is to control the functioning of a cell. Additionally, human DNA is chemically identical to DNA from other organisms (including bacteria); so, human and bacteria DNA are indistinguishable from each other. Because this is true, researchers have learned a great deal about the human genome from other organisms. Moreover, researchers can combine sequences from bacteria DNA with human DNA in order to form a new sequence with a specific desired function (called recombinant DNA). An example of this would be combining a sequence from one organism that instructs a cell to continually make protein with a sequence from human DNA creating a specific protein that may not be functioning properly, thus fixing mistakes in sequences. Researchers can also create strands of DNA, called cDNA, that contain only the parts of the strand that are expressed and used by the cell to make proteins and remove the non-essential parts. Recombinant DNA, cDNA, isolated DNA (which is the chemical extracted from the cells of an organism, and copied in the lab), and processes of isolating genes are all patentable. All of these genes, recombinant DNA, cDNA, and isolated DNA, are molecules that have a specific chemical structure. Thus, a gene patent is legally just a chemical patent, such as a patent on a drug.
Gene Fragments/ESTs: ESTs, or Express Sequence Tags, are gene fragments that are 300 to 500 bases long. ESTs can be useful because they can be used as tools to help researchers find the entire gene associated with that tag.
SNPs: SNPs, or single nucleotide polymorphisms, are variations in the DNA sequence that occur when a single nucleotide (A, T, C, or G) in the sequence is altered. These are points in the human genome that can exist as two different versions (alleles), and occur every 100 to 1,000 bases along the 3-billion-base human genome. There are around 1,000,000 SNPs in the genome. SNPs are valuable to researchers because they are used as frequent, informative markers when making a genetic map. SNPs are also important to researchers because of how variations can affect disease in individuals. Some SNPs can have an affect on a disorder, such as in Cystic Fibrosis, or may cause a disorder, such as sickle cell anemia. Others are unrelated to disease and are just normal variations in the base sequence of the human genome. In the case of cancer, identifying different SNPs on a SNP map can help researchers understand which genes contribute to the disease and develop possible treatments – which is both valuable and patentable.
Gene Tests: Any gene test, including carrier screening, disease diagnosis testing, predisposition testing, and newborn screening, can be patented. The tests are all based on the genes associated with the disease.
Proteins: DNA essentially programs the body to create proteins. Proteins carry out instructions based on the sequences of the amino acids within DNA. Proteins, such as hormones, enzymes, and antibodies, are responsible for the structure, function, and regulation of the body. Researchers use proteins because they indicate which genes are being used and how they are being used. This information is important when designing drugs because drugs interact with proteins. Patenting proteins is useful to researchers who use them as a link between the genetic disease and drug development.
Methods of Treatment: Methods of treatment, such as gene therapy, are patentable because procedures are patentable. Methods of treatment can be very complex and require many steps that involve modifying genes associated with a disease.
Canavan Disease and the Case of Greenberg v. Miami Children’s Hospital
Soon after the Greenberg’s son Jonathan was born in 1981, they realized something was wrong. At three months, their baby was having problems with motor skills. Six months, and many doctors later, Jonathan was diagnosed with Canavan disease – an incurable degenerative disease that results in childhood death. Canavan disease affects mainly Jews of Central and Eastern European descent (see Canavan disease). The Greenbergs later had a second child, Amy, who was also born with Canavan disease.
The Greenbergs became involved with preventing Jewish genetic disorders, specifically Tay-Sachs screening, and founded the Chicago chapter of National Tay-Sachs and Allied Diseases Association (NTSAD). Through NTSAD they met Dr. Reuben Matalon, a researcher at University of Illinois at Chicago, and, in 1987, convinced him to focus on Canavan disease. They hoped to make carrier and prenatal testing available for Canavan disease, as it was for Tay-Sachs: accessible and affordable for the public.
Tissue samples from their children were donated to the research effort. The Greenbergs also founded the Canavan Registry to track samples from other children, considered to be integral to finding the gene. Dor Yeshorim, a testing program for Jewish genetic disorders, joined the effort. Over 160 families gave samples.
In 1993, Dr. Matalon, now at Miami Children’s Hospital, identified the Canavan gene. In 1996 the Canavan Foundation began to offer free testing. By 1997, Miami Children’s Hospital received a patent on the gene without telling those involved in donating tissue samples that they had applied for a patent, including the Greenbergs. Canavan Foundation was forced to stop offering free screening after being faced with license requirements from the patent.
In 1998, the American College of Obstetricians and Gynecologists recommended that all women of Ashkenazi Jewish descent have carrier screening for Canavan disease. Soon thereafter, Miami Children’s Hospital began to enforce its patent. It charged $25/test for every lab participating in the screening. For each lab, this meant an additional $25 surcharge (per test) added to the costs of performing the actual test. They eventually reduced the charge by half.
In addition to royalties, Miami Children’s Hospital (MCH) restricted not only the number of labs that could perform tests but also the number of tests that could be administered each year, possibly in the hopes that a large company would be attracted by this limitation and apply for an exclusive license. Unfortunately, this backfired, and some labs dropped the testing altogether. Additionally, the hospital and researchers failed to obtained informed consent from the families.
On October 30, 2000, legal clinics at the Chicago-Kent College of Law filed a pro-bono lawsuit against the hospital and Dr. Matalon on behalf of parents of children with Canavan disease (who participated in the Canavan Registry), Canavan Foundation, Dor Yeshorim, and NTSAD. The suit alleges that Dr. Matalon and MCH secretly obtained a patent for the Canavan disease gene using the financial resources and genetic material from the families and began to limit access to testing with licensing and royalties. The lawsuit, the first of its kind, alleges breach of informed consent, breach of fiduciary duty, unjust enrichment, fraudulent concealment, conversion, and misappropriation of trade secrets. The case was filed in Federal District Court in Chicago, but it recently has been transferred to a federal district court in Florida.
For more information see:
Kent Law at
Chicago Tribune at
Canavan Foundation at
Salon.com article at
“Owning a Piece of Jonathan”
by Lucinda Hahn, copyright Chicago magazine, May 2003
(For a copy of this article, please contact the Center)
Myriad Genetics and BRCA1 and 2
Myriad Genetics, a Utah-based biotech company, has faced challenges internationally with its patents. Myriad is the owner of the rights to two genes associated with hereditary breast cancer: BRCA1 and BRCA2. These genes normally help to restrain cell growth; the mutated versions, however, predispose a person toward developing breast cancer, usually at an earlier age than the general population.
Myriad discovered the BRCA1 gene in 1994 and the BRCA2 gene in 1996. By 1998 they had received patents on both. Myriad now owns over seven foreign patents and over six U.S. patents covering the BRCA1 and BRCA2 breast and ovarian cancer genes and their use in the development of therapeutic and predictive medical products.
In 1998, shortly after receiving its patent on the BRCA2 gene, the company settled a patent infringement case against OncorMed. Myriad obtained OncorMed’s entire BRCA1 and 2 Genetic Testing Program including all testing services, all contacts, all customer lists, exclusive licenses for all current and pending patents, and a financial settlement.
In January 2001, Myriad won a European patent giving the company control over testing for mutations of the BRCA1 gene in Europe. Shortly thereafter, a Parisian research center filed an action with the European Patent Office against Myriad over the breadth of the patent. Several European researchers had already developed their own tests, which detect partial deletions of genes and other factors contributing to breast and ovarian cancers, which Myriad’s tests do not detect. Additionally, some of these researchers were able to offer their tests for a third of Myriad’s $2,580 test. Potentially, researchers could be concerned that the breadth of a patent, like Myriad’s, might restrict other related research.
In the United States, concerns are similar. American researchers must pay a patent cost to Myriad of $2,680 to use the tests, except for NIH-funded academic researchers who pay only $1,200 per test. Any research crossing into commercial use violates the patents and researchers faced with the high costs of the tests have abandoned their research in some cases. Additionally, physicians are required to send their patients’ blood to a single location – Myriad’s headquarters – for testing so the company can insure quality control.
However, Myriad keeps a database of over 800 mutations, which it posts online for the public and researchers. Myriad is presently researching other mutations and ways to detect gene deletions. They would like to make a comprehensive test for all inherited breast cancers. The company is also mapping the proteome to find out what all the proteins encoded by the genome are and their functions.
Currently, the European action filed by the Institute Curie, with 17 French hospitals and research associations and with the official backing of the French government, is still pending. The Belgian and Dutch governments are also supporting the action.
To learn more about Myriad’s BRCA1 and BRCA2 story, visit:
The Boston Globe Magazine at
Buiness2.0 article at
Technology Review article at http://lists.essential.org/pipermail/ip-health/2001-December/002521.html
Institut Curie www.curie.fr or www.curie.net
Myriad Genetics (see the press releases) at http://www.myriad.com
On Their Own Terms: How PXE Families Protected Themselves
In 1994, seven-year-old Elizabeth Terry and her five-year-old brother Ian were diagnosed with pseudoxanthoma elasticum (PXE), a genetic disorder that can cause connective tissue in the eyes, arteries, and skin to calcify. Complications can vary from very mild to severe, although the Terry family did not know this at the time.
In fact, in 1994, little was known about PXE, and based on the available literature, PXE was considered often to be fatal. The Terrys found this out soon after the diagnosis when they went to a medical library and read as many articles about PXE as they could find. They realized that there was not a great deal of information known about the disease; they knew more research needed to be done.
Soon after the diagnosis, researchers called to get blood samples from the children, but the Terrys felt that the researchers were only interested in the disease and not concerned with the patients. This motivated them to start a website and a support group. They also began to research how to create a tissue sample repository. With the help of a friend at a law firm, they created a non-profit group, PXE International. In 1996, Testa, Hurwitz & Thibeault incorporated PXE international and provided them council on their tissue bank and patenting, pro-bono. They also received advice from Elizabeth Thomson at the National Human Genome Research Institute about how to set up the sample repository, informed consent, and how to create guidelines on how researchers could use the material.
The Terrys traveled around, collecting tissue samples from all the PXE sufferers they could find, and added them to their tissue repository. Next, they began to recruit researchers by telling them about the tissue repository and data they had collected. When they found research teams interested in the samples, they had the researchers sign contracts that would allow PXE International to be named in the patent application and share any profits resulting from the discovery of the PXE gene.
In February 2000, researchers at the University of Hawaii isolated the gene and listed PXE International on the patent application. Fortunately, the Terrys had a good relationship with the researchers and the researchers had relied on information the Terrys gave them at the beginning and throughout the process. The University was reluctant to share the patent and licensing arrangements, but the Terrys paid for filing costs with PXE International’s budget, and worked out licensing agreements with the University that worked for both parties.
Today, the Terrys are still active and lobby for patients rights in Congress. Much more is now known about PXE, and many patients live normal lives. PXE has also begun to serve as a model for other groups who want to keep genetic information accessible and costs low.
For more information, visit:
PXE International at http://www.pxe.org/
Testa, Hurwitz & Thibeault, LLP at
MSN Health with WebMD at
Johns Hopkins University and Genzyme: Striking a Balance
Striking a balance between academic and commercial research, Johns Hopkins University attempted to encourage research in both sectors when it patented a technique, known as SAGE, to locate genes involved in diseases. The school created a license that gave all commercial rights to a single company, Genzyme Corporation with an agreement that also allows Johns Hopkins to authorize use of the technology to academic researchers. Around 300 academic labs use the process without having to worry about patent infringement or paying licensing fees. Johns Hopkins was able to make money for itself through the license to Genzyme, and Genzyme can profit because they are the only commercial company using the process. Additionally, independent research can still be conducted on a large scale.
Ask Questions and Protect Yourself
For researchers and those looking for answers about debilitating genetic diseases, learning about patenting and the controversy surrounding it can be very useful. Knowing what the issues are and what has taken place in the past can help researchers protect themselves from patent infringement and families protect themselves from scenarios like the Canavan disease lawsuit.
Many questions have arisen about the implications for medicine and society if private corporations own the rights to use our genes. Should a single person or company decide who should be tested? At what point during their research should scientists be able to patent sequences? Should university researchers be able to use patented information without infringing on patents? Should patients be afforded better protection by federal law in the case of patented tests?
Many more questions remain, and as patenting in genetics proceeds, new questions will continue to arise. The best way to protect yourself is to stay informed.
Some suggestions for families becoming involved with genetic research are:
Monitor the Situation
On the Federal level, bills have been introduced in the House on these issues. Companies and organizations, such as Bio and the American Medical Association, follow these issues, make recommendations, and lobby congress.
On March 14, 2002, Rep. Lynn Rivers (D-Mich.), introduced the “Genomic Research and Diagnostic Accessibility Act of 2002” (H.R. 3967) and the “Genomic Science and Technology Innovation Act of 2002” (H.R. 3966). The first bill would allow physicians to perform testing without infringing on a patent and would also allow researchers to use patented genetic information for non-commercial research. The second bill would direct the Office of Science and Technology Policy to conduct a study on the impact of Federal policies on the innovation process for genomic technologies. The bills have both been referred to the House Judiciary Committee and H.R. 3966 has also been referred to the House Sciences Committee.
Find more information about the bills:
Visit the House Committee of Science Democratic Caucus at
http://www.house.gov/science_democrats/member/lr031402.htm to read the bills and the congressional record.
Visit the Office of Legislative Policy Analysis (OLPA) at the NIH at http://olpa.od.nih.gov/ to read a backgrounder on the bills, their major provisions, and their status and outlook. This is also a great resource to track genetic and health legislation in general.
For more information on these bills, visit our section on Advocacy!
Or, to learn about policy and advocacy regarding genetic patenting:
Visit the American Medical Association at http://www.ama-assn.org/ama/pub/category/1830.html
Or Bio.org for the Biotech Industry view at http://www.bio.org/ip/
Find Abstracts and Full Text of Patents
Researchers can use Patent and Trademark Depository Libraries and other databases to read patents applications and other information about patents. Germany, the United Kingdom, and Japan are also very strong in genetic research and gene patenting. Abstracts and full texts of patents from these countries can be found online; the European Patent Office, Japanese Patent Office, and USPTO issue the most gene-related patents.
U.S. Patent & Trademark Office Searchable Patent Database
DNA Patent Database
The Kennedy Institute of Ethics at Georgetown University and the Foundation for Genetic Medicine sponsor a project to provide free public access to the full text and analysis of DNA patents by the U.S. Patent and Trademark Office (PTO).
Entrez and GenBank are located here. Both are free database of all the genome sequences generated by the Human Genome Project and any other publicly available sequences.
Human Chromosome Launchpad
A single-source launchpad to information about each human chromosome. Each chromosome page provides links to gene maps, sequences, associated genetic disorders, nonhuman genetic models, identified genes, research efforts and laboratories, and other information as available.
dbSNP is a GenBank-independent database for SNP information.
Get More Information/Links
American Medical Association
Gene Letter – Patenting DNA: A Primer
Genome and Genetic Research, Patent Protection and 21st Century Medicine-a comprehensive primer from Bio.org (The Biotechnology Industry Organization)
Human Genome Project Information on Genetics and Patenting- one of the most useful and comprehensive websites on gene patenting.
World Intellectual Property Organization- nicely designed and informative
Books About Patenting
Written September, 2002.
Thank you to Tim Holbrook, Assistant Professor of Law, Chicago-Kent College of Law, who reviewed this article.
Last Update: 11/02