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Primer

Primer: Genome and Genetic Research, Patent Protection and 21st Century Medicine

Introduction

The gyrations of biotechnology stocks in recent months, together with the recent completion of draft sequences of the human genetic code, have focused renewed public and media attention on the enormous importance and future promise of modern biotechnology. The Biotechnology Industry Organization (BIO) receives many questions from individuals, Congress, patient advocacy organizations and media outlets about patents and how they apply to biotechnology. This primer is intended to address these questions.

Strong protection for intellectual property is as essential in this area as it is in most other cutting-edge fields of endeavor. This document is intended to provide non-experts with a clear, straightforward explanation of the principles behind patents and how they apply in biotechnology, especially how they apply to genomic research. Biotechnology patents can serve to encourage the development of new medicines, diagnostics and agricultural products.

BIO represents more than 1,000 biotechnology companies, academic institutions and state biotechnology centers in all 50 states and more than 33 nations. We represent the industry in its dealings with Congress and the administration, with state and local governments, and with the public and the media.

Please contact us at BIO with any questions or for additional information on the topics discussed in this document. We can be reached at (202) 962-9200 (voice) or at (202) 962-9201 (fax).

What is a patent?

A patent is an agreement between the government and an inventor whereby, in exchange for the inventor's complete disclosure of the invention, the government gives the inventor the right to exclude others from using the invention in certain ways. Note that the property right provided in a patent is quite different from what we typically think of when we own property. What is granted is not the right to make, use, offer for sale, sell or import, but the right to stop others from making, using, offering for sale, selling or importing the invention.

Types of Patents
Three types of patents exist: utility, design and plant patents. Utility patents are granted to those who invent or discover new and useful machines or processes, while design patents are issued to inventors of new, original and ornamental design for an article of manufacture. Plant patents are given to those who invent or discover, then asexually reproduce a new plant type.

Patent Protection in the Constitution
A patent grants exclusive rights to inventors for limited periods. The first law providing exclusive rights to the makers of inventions for limited time periods seems to have been in Italy in the 15th century. Even before the signing of the Federal Constitution of the United States, most states had their own patent laws. The U.S. Constitution entrusted Congress to provide protection for inventions. The basis for the federal patent and copyright systems is found in the Constitution of the United States, Article 1, Section 8, Clause 8, which states:

Congress has enacted various laws relating to patents. The first U.S. patent law was enacted in 1790. Today, in the United States, patents are granted by the U.S. Patent and Trademark Office (PTO) and are effective only within the United States and its territories. The term of a new patent is 20 years from the date on which the application for the patent was filed in the United States or, in certain cases, from the date an earlier, related application was filed.

What is the purpose of a patent?

The rationale for a patent system is to provide an advantage to society as a whole by rewarding the development of new inventions. Thus, the patent system has two basic purposes: to promote the advancement of technology and to protect the inventor.

Promoting Technological Advancement
The patent system provides a process for the disclosure of valuable information that can stimulate research across the globe. To obtain a patent, an inventor must "teach" the public how to make and use the invention in the best way the inventor knows. Thus, the patent system rewards only those inventors who are willing to share their inventions with the whole world.

Moreover, the information disclosed in a patent application is usually available to the public long before a patent issues. If a patent application is filed internationally or (from 2000 onwards) in the United States, it is published 18 months after its initial filing. The exception to this rule is that an applicant who has filed only in the U.S. and not abroad may request that the U.S. application not be published. If however, the applicant files in a foreign country, then the U.S. patent application will be published. Once published, a patent application and all its information are available to anyone. Thus, the patent system greatly stimulates the flow of scientific and technological knowledge. That's why societies that protect inventors with patents are the world's most advanced, scientifically and technologically.

What can be patented?

Under U.S. law, various types of invention can be patented. These are:

• A process - for example, a process of making a chemical by combining chemical X with chemical Y, or a method of treating a cancer patient by administering a specific drug.
• A machine - for example, a flat-screen high-definition television set or an X-ray machine.
• An article of manufacture - for example, a silicon computer chip or a specially molded piece of plastic for an automobile bumper.
• A composition of matter - for example, a new pharmaceutical drug or a new plastic for use in kitchen counters.
• Any new and useful improvement to an invention that falls under any of these categories.

Other types of inventions or discoveries cannot be patented; these include naturally occurring organisms, laws of nature, natural or physical phenomena, and abstract ideas.

Biotechnology Patents
Biotechnology inventions generally fall into one of two classes:
1) New compositions of matter related to newly discovered isolated genes or proteins or to pharmaceutical inventions based on those genes or proteins. One cannot patent a naturally occurring gene or protein as it exists in the body, but one can patent a gene or protein that has been isolated from the body and is useful in that form as a pharmaceutical drug, screening assay or other application.

2) Methods of treating patients with a given disease through the use of a particular gene or protein. Even if someone has a patent on a gene or protein, a second inventor can obtain a patent on a new use of that gene or protein, if the second inventor discovers a new use for the substance.

What must an inventor show to get a patent?

To obtain a patent on a new invention, an inventor must show that these three criteria are met:

1. The invention is novel and nonobvious: that is, the invention is really new. The invention must not have been described or discovered by another before the inventor filed a patent application. The invention must also not be obvious from the prior work of others. In patenting a gene or a protein, the requirement for novelty and nonobviousness usually means that the inventor must know the chemical structure of the new gene or protein. If that structure already is known, the inventor can't meet this requirement.
2. The invention is useful. The inventor must show that the invention has a real-world use. It isn't enough just to find a new gene or protein. The inventor must specify what the uses are; for example, whether the gene or protein is useful as a drug for disease X or as a target for disease Y or as a diagnostic marker for disease Z.
3. The application describes the invention in sufficient detail to allow the public to make and use the invention. The inventor must teach or "enable" other persons that are skilled in the technological area of the invention to use the invention described by the inventor.

In addition to the above criteria, a description of the material or tool for which a patent is sought cannot have been published in print, here in the United States or abroad. Also, if the invention has been on sale or in use in this country for a year before the application is filed, a patent will not be awarded to the invention.

What must an inventor include with a patent application?

To obtain a patent, the inventor is required to submit a patent application to each country in which he or she desires to obtain patent protection. In the United States, a complete patent application must contain the following components:

1. A written English language document (called the specification) that clearly describes and explains the invention. Attached to the specification must be at least one "claim" that sets forth the desired legal parameters of the claimed invention.
2. A drawing illustrating the invention, if such a drawing is necessary for understanding the invention.
3. An oath or declaration by the inventor(s) claiming inventorship.
4. A filing fee (about $700, or more, depending on the patent application).

Can living things be patented?

Some living things can be patented, but not all. Like any invention, a living thing must be "new" in order to be patented. More importantly, living organisms under consideration for patenting cannot be those that occur or exist in nature. Thus, one cannot obtain a patent on just any living creature, such as a mouse, because mice have been around for a long time. If someone makes a kind of mouse that never existed before, however, then that kind of mouse might be patented. For example:

• Microbes: As long ago as 1873, Louis Pasteur received a U.S. patent for yeast "free from organic germs or disease." With the growth of genetic engineering in the late 1970s, the patentability of living organisms was re-examined, and confirmed. A landmark case involved Ananda Chakrabarty's invention of a new bacterium genetically engineered to degrade crude oil. In 1980, the Supreme Court clearly stated that new microorganisms not found in nature, such as Chakrabarty's bacterium, were patentable. Chakrabarty received a patent in 1981 (U.S. Pat. No. 4,259,444). In the Chakrabarty decision, the Supreme Court stated that "anything under the sun that is made by the hand of man" is patentable subject matter. Therefore, if a product of nature is new, useful and nonobvious, it can be patented if it has been fashioned by humans.
• Plants: In 1930, the U.S. Congress passed the Plant Patent Act, which specifically provided patent protection for newly invented plants that are asexually reproduced. In 1970, Congress provided similar protection for newly invented sexually reproduced plants.
• Animals: In the 1980s, the question of whether multicellular animals could be patented was examined. The key case involved a new kind of "polyploid" oyster that had an extra set of chromosomes. This new, sterile oyster was edible all year round because it did not devote body weight to reproduction during the breeding season. The PTO found that such organisms were in fact new and therefore eligible for patenting. It found this particular type of oyster to be obvious, however, and thus did not allow a patent for it. Nonetheless, the polyploid oyster paved the way for the patenting of other nonnaturally occurring animals. In 1988, Philip Leder and Timothy Stewart were granted a patent on transgenic nonhuman mammals (U.S. Pat. No. 4,736,866) that covered the so-called Harvard mouse, which was genetically engineered to be a model for the study of cancer.
• Natural Compounds: Natural compounds, such as a human protein or the chemical that gives strawberries their distinctive flavor, are not themselves living, but occur in nature. Thus, they are new and can be patented only if they are somehow removed from nature. Therefore, a compound that is purified away from a strawberry, or a protein that is purified away from the human body can be patented in its purified state. Such a patent would not cover the strawberry or the person. The U.S. PTO does not allow anyone to patent a human being under any circumstances.

What is a gene?

A gene is the fundamental physical and functional unit of heredity that is made up of tightly coiled threads or polymers of deoxyribonucleic acid (DNA). A DNA molecule consists of two strands that wrap around each other to resemble a twisted ladder or double helix. DNA is an informational molecule and is made up of four distinct nucleotides: deoxyadenosine (A), deoxyguanosine (G), deoxythymidine (T), and deoxycytidine (C). It is the nonrandom order of these individual "bases" that results in DNA being an informational molecule. However, in and of itself, DNA has no functional property. It is a chemical that, when placed in an appropriate environment, will direct the synthesis of particular and specific proteins, which make up the structural components of cells, tissues and enzymes (molecules that are essential for biochemical reactions). This environment is found within the cell. Organisms, from single-celled protozoans to far more complex human beings, are made up of cells containing DNA and associated protein molecules. The DNA is organized into structures called chromosomes, which encode all the information necessary for building and maintaining the organism. A DNA molecule may contain one or more genes, each of which is a specific sequence of nucleotide bases. It is the specific sequence of these bases that provides the exact genetic instructions that give an organism its unique traits.

Patented Genes
Isolated and purified genes are patentable inventions if they meet the PTO's standard criteria, including being novel, well described and useful.

Gene-based patents have helped attract the biotechnology and pharmaceutical industry's interest in the development of gene-based therapeutics. For example, the gene that encodes erythropoietin was cloned in 1985, which led to the production of recombinant EPO (Rhu-EPO). Amgen patented this gene in 1987. The protein expressed by this gene is used in the treatment of anemia arising from several diseases.

Introns, Exons and Genomes
A "genome" is the complete set of genetic instructions carried within a single cell of an organism. (A gene, in contrast, is a small subunit of the genome that in general "codes for"-that is, contains the information necessary for constructing-a single protein or protein subunit.) The human genome is estimated to comprise between 30,000 and 40,000 genes. Only about 3 percent of the human genome is known to include the protein-coding sequences (exons) of genes, and many genes are interrupted by sequences that have no coding function (introns). For a gene to be correctly made into a protein, these introns must be removed and the exons must be precisely spliced together.

How will the discovery of new genes help society?

Many, if not most, human diseases have their roots in our genes. More than 4,000 diseases are suspected to stem from mutated genes inherited from one or both parents. As of April 2000, 1,792 individual genes had been linked to disease, including common disorders such as heart disease and many cancers. These discoveries hold promise for new treatments.

Genes as Disease Carriers
Genes come in pairs, with one copy inherited from each parent. Many genes come in a number of variant forms, known as alleles. A dominant allele prevails over a normal allele. A recessive allele becomes apparent only if its counterpart allele becomes inactivated or lost. For example, in cystic fibrosis, the altered gene that causes abnormal mucus production and disease is a recessive allele. A person who inherits one copy of the recessive allele does not develop the disease because the normal allele predominates. Such a person is a carrier, however, and has a 50 percent chance of passing the recessive allele to his or her descendants. When both parents are carriers, the chance is one in four that a child will inherit two of the recessive alleles, one from each parent, and so develop the disease.

Predictive Gene Tests
Once scientists have linked a gene to a disease, predictive gene tests can be developed and used to identify individuals who are at risk of getting the disease, even before any symptoms appear. The most widespread type of genetic testing, newborn screening, can detect abnormal or missing gene products that might indicate a birth defect. Carrier testing can be used to help couples learn if they carry-and thus risk passing to their children-a recessive allele for inherited disorders. Doctors use genetic tests to identify telltale DNA changes in cancer or precancerous cells. Such tests can be helpful in several areas. These include early detection (for example, familial adenomatous polyposis genes prompt close surveillance for colon cancer); diagnosis (different types of leukemia can be distinguished); prognosis (the product of a mutated p53 tumor-suppressor gene flags cancers that are likely to grow aggressively); and treatment (antibodies block a gene product that promotes the growth of breast cancer).

Predictive gene tests have been or are being developed for diseases such as Tay-Sachs disease, cystic fibrosis, amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), Huntington's disease, some forms of Alzheimer's disease, catastrophically high cholesterol, and several types of inherited cancer.

Gene Therapy
The discovery of genes and gene markers will provide invaluable tools for improving disease prediction, diagnosis and treatment. By spotting a mutated gene (or its protein product) in cells, doctors may be able to detect disease years earlier than with clinical or symptom-based diagnostic techniques. If a gene product is found to protect against a particular disease, it might be possible to synthesize that protein and use it as a drug or to find a drug that will interact with the protein to treat the disease. Ultimately, it may be possible to thwart disease with gene therapy-inactivating the flawed gene or replacing it. In this type of therapy, a gene may itself be a drug.

Animal and Microorganism Gene Patents
Patents for genes from nonhuman animals already exist. These patented genes help to provide a basis for the study of human diseases and a correlation for the discovery of related genes in humans. Many animal oncogenes have been used to provide a link to specific cancers in humans. For example, the rat neu oncogene was the preview to the human Her-2 oncogene. The discovery of this rat oncogene and later the human counterpart enabled researchers to create diagnostic tests for cancer.

Genetic materials from microbes are also patentable and are valuable diagnostic tools for disease detection and identification. For example, the entire HIV genome has been sequenced and patented. Although many diagnostic tests employ proteins as reagents, the genetic material of pathogenic microorganisms is useful for recombinantly expressing pathogen-specific proteins as well as for use as a diagnostic tool at the genomic level.

Agricultural Innovations
Agricultural biotechnology is another area where patent protection has been and continues to be valuable. The development of disease-resistant varieties of cucumbers, squash, melons and pumpkins is a perfect example of how the patent system promotes dissemination of information for future research and development. Additionally, there are patents that cover production of mammalian proteins in plants and plant cells, that is, plant bioreactors and methods of making sterile plants by recombinant techniques. There are also patents that cover transgenic plants that exhibit salt resistance and increased tolerance to drought. With an ever-expanding human population, coupled with increasingly scarce agricultural resources, agricultural innovation is essential.

Why should patients care about patents?

Patents encourage companies to invest in discovering drugs. Developing a new medicine is an extremely expensive and risky process that takes many years. It usually entails performing years of research and conducting clinical studies at multiple centers, a necessary safeguard for the public that nevertheless imposes heavy burdens, especially for small companies. Companies spend, on average, more than $800 million to develop a drug. In fact, of the 1,000-plus companies and research institutions represented by BIO, only 5 percent are profitable.

If there were no patent protection, competitors would immediately copy and sell an innovative drug as soon as it was approved for sale, thus avoiding the development costs. Because the competitors would have lower costs, they could capture the market by offering the drug at a lower price. In this situation, the innovator would never recover the development costs. Thus, without patents, companies would be reluctant to invest in research and drug discovery programs.

Modern biotechnology offers unprecedented opportunities for developing medicines to treat and cure currently intractable diseases. It relies in large part on using gene-based inventions to make these medicines because it is either impossible or uneconomical to make them in other ways. Patents on such inventions protect them from misappropriation by commercial entities and allow a company to have confidence that it can service a viable market if its development efforts succeed. Without patents on gene-based inventions, the rate of medical innovation coming from biotechnology would slow dramatically. Ultimately, patients would be deprived of new therapies.

Are patents granted on an individual's genes?

No, patents do not provide any rights to a person or the genes in his or her body. Instead, patents are granted on "isolated" genes and gene products that have real-world applicability. That is, the patents cover genes and gene products that could be obtained from any person, for example, from a blood sample. As previously mentioned, patents may also cover genes of microbes as well as genes from animals and plants.

When considering the patentability of nucleic acids, which are the building blocks of genes, one must take into account the nature of the object patent for which protection is being sought. A nucleic acid, regardless of its source, is chemically indistinguishable from any other nucleic acid. While its sequence of bases may change, there is no a priori means of establishing its source. Human DNA is no different, at least chemically, from that of a bacterium. If one were presented with a nucleic acid, its sequence could be chemically characterized, and any protein that it might encode could be determined. However, it would not be possible to ascertain what species the DNA came from. In fact, DNA as an isolated molecule does not exist within living cells. It is always associated with various other molecules, such as proteins, sugars and fats. It is well established that subject matter that is a product of nature is not eligible for patent protection. However, isolated nucleic acids do not exist in nature.

What does a patent say or provide?

Biotechnology inventions relate to new and nonobvious compositions of matter and/or new and nonobvious methods of making or using novel or known compositions of matter (see "What can be patented?").

The following issued claims exemplify the numerous ways in which patent protection relating to a protein may be obtained (erythropoietin is a protein, essential in red blood cell formation, that had previously been isolated from human urine):

U.S. Patent No. 5,621,080
1. An isolated erythropoietin glycoprotein having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells, wherein said erythropoietin glycoprotein comprises the mature erythropoietin amino acid sequence of FIG. 6 and has glycosylation which differs from that of human urinary erythropoietin.

U.S. Patent No. 6,048,971
1. A secretable mutant human erythropoietin protein having an amino acid residue which differs from the amino acid residue present in the corresponding position in wild type human erythropoietin, the amino acid residue of said wild type erythropoietin selected from the group consisting of: amino acid residue 103, amino acid residue 104, and amino acid residue 108.

U.S. Patent No. 5,955,422
1. A pharmaceutical composition comprising a therapeutically effective amount of human erythropoietin and a pharmaceutically acceptable diluent, adjuvant or carrier, wherein said erythropoietin is purified from mammalian cells grown in culture.

U.S. Patent No. 4,703,008
1. A purified and isolated DNA sequence encoding erythropoietin, said DNA sequence selected from the group consisting of: a. the DNA sequences set out in FIGS. 5 and 6 or their complementary strands; and b. DNA sequences which hybridize under stringent conditions to the DNA sequences defined in (a). & 4. A prokaryotic or eukaryotic host cell transformed or transfected with a DNA sequence according to claim [1] in a manner allowing the host cell to express erythropoietin.

U.S. Patent No. 5,618, 698
1. A process for the preparation of an in vivo biologically active erythropoietin product comprising the steps of:

1. growing, under suitable nutrient conditions, host cells transformed or transfected with an isolated DNA sequence selected from the group consisting of (1) the DNA sequences set out in FIGS. 5 and 6, (2) the protein coding sequences set out in FIGS. 5 and 6, and (3) DNA sequences which hybridize under stringent conditions to the DNA sequences defined in (1) and (2) or their complementary strands; and
2. isolating said erythropoietin product therefrom.

U.S. Patent No. 5,641,670
1. A homologously recombinant cell having incorporated therein a new transcription unit, wherein the new transcription unit comprises an exogenous regulatory sequence, an exogenous exon and a splice-donor site, operatively linked to the second exon of an endogenous gene, wherein the homologously recombinant cell comprises said exogenous exon in addition to exons present in said endogenous gene.

10. The homologously recombinant cell of claim [1] wherein the endogenous gene encodes a protein selected from the group consisting of erythropoietin, calcitonin, growth hormone, insulin, insulinotropin, insulin-like growth factors, parathyroid hormone, beta-interferon, gamma-interferon, nerve growth factors, FSH-beta, TGF-beta, tumor necrosis factor, glucagon, bone growth factor-2, bone growth factor-7, TSH-beta, interleukin 1, interleukin 2, interleukin 3, interleukin 6, interleukin 11, interleukin 12, CSF-granulocyte, CSF-macrophage, CSF-granulocyte/macrophage, immunoglobulins, catalytic antibodies, protein kinase C, glucocerebrosidase, superoxide dismutase, tissue plasminogen activator, urokinase, antithrombin III, DNAse, alpha-galactosidase, tyrosine hydroxylase, blood clotting factor V, blood clotting factor VII, blood clotting factor VIII, blood clotting factor IX, blood clotting factor X, blood clotting factor XIII, apolipoprotein E, apolipoprotein A-I, globins, low density lipoprotein receptor, IL-2 receptor, IL-2 antagonists, alpha-1 antitrypsin, immune response modifiers, and soluble CD4.

U.S. Patent No. 6,048,524
1. A method of expressing erythropoietin in a mammal, comprising the steps of:

1. obtaining a source of primary cells from a mammal;
2. transfecting primary cells obtained in (a) with a DNA construct comprising exogenous DNA encoding erythropoietin and additional DNA sequences sufficient for expression of the exogenous DNA in the primary cells, thereby producing transfected primary cells which express the exogenous DNA encoding erythropoietin;
3. culturing a transfected primary cell produced in (b), which expresses the exogenous DNA encoding erythropoietin, under conditions appropriate for propagating the transfected primary cell which expresses the exogenous DNA encoding erythropoietin, thereby producing a clonal cell strain of transfected secondary cells from the transfected primary cell;
4. culturing the clonal cell strain of transfected secondary cells produced in (c) under conditions appropriate for and sufficient time for the clonal cell strain of transfected secondary cells to undergo a sufficient number of doublings to provide a sufficient number of transfected secondary cells to produce erythropoietin; and
5. introducing transfected secondary cells produced in (d) into a mammal of the same species as the mammal from which the primary cells were obtained in sufficient number to express erythropoietin in the mammal.

U.S. Patent No. 4,397,840
1. A method for the preparation of an erythropoietin product having no inhibitory effect against erythropoiesis which comprises the steps of:

1. adsorbing a crude erythropoietin product obtained from the urine of healthy human on to a weakly basic anion exchanger from a neutral or weakly acidic aqueous solution in the presence of an inorganic neutral salt in a concentration in the range from 0.1 to 0.2 mole per liter, and
2. eluting the thus adsorbed erythropoietin product with an aqueous eluant solution containing an inorganic neutral salt in a concentration in the range from 0.5 to 0.7 moles per liter.

U.S. Patent No. 4,667,016
1. A process for the efficient recovery of erythropoietin from a fluid, said process comprising the following steps in sequence: subjecting the fluid to ion exchange chromatographic separation at about pH 7.0, thereby to selectively bind erythropoietin in said sample to a cationic resin; stabilizing materials bound to said resin against degradation by acid activated proteases; selectively eluting bound contaminant materials having a pKa greater than that of erythropoietin by treatment with aqueous acid at a pH of from about 4.0 to 6.0; and selectively eluting erythropoietin by treatment with an aqueous salt at a pH of about 7.0; and isolating erythropoietin-containing eluent fractions.

U.S. Patent No. 6,001,800
1. A method for preparing spray dried recombinant human erythropoietin (rhEPO), comprising:

1. providing an aqueous solution of rhEPO having a concentration within the range of about 20 mg/ml to about 100 mg/ml;
2. atomizing said solution into a spray;
3. drying said spray with hot drying air in order to evaporate the water from the spray to form a dried rhEPO; and
4. separating dried rhEPO from the drying air to provide biologically active spray dried rhEPO.

U.S. Patent No. 5,629,175
1. A method for producing a mammalian peptide which comprises: growing tobacco plant cells containing an integrated sequence comprising, a first expression cassette having the direction of transcription (1) a transcriptional and translational initiation region functional in said plant cells, (2) a structural gene coding for said mammalian peptide, and (3) a termination region, whereby said structural gene is expressed to produce said mammalian peptide.

U.S. Patent No. 5,780,709
A method to increase water stress resistance or tolerance in a monocot plant, comprising: introducing into cells of a monocot plant an expression cassette comprising a preselected DNA segment comprising an mtlD gene, operably linked to a promoter function in the monocot plant cells to yield transformed monocot plant cells; and b) regenerating a differentiated fertile plant from said transformed cells, where in the mtlD gene is expressed in the cells of the plant so as to render the transformed monocot plant substantially tolerant or resistant to reduction in water availability that inhibits the growth of an untransformed monocot plant.

As exemplified above, it is likely that patents directed to related compositions of matter and/or distinct methods corresponding to these compositions will issue to multiple parties. In situations where party A has been granted a patent directed to composition X and party B has been granted a patent having claims directed to a new use of composition X, party A may preclude others (including party B) from making, using or selling compound X, whereas party B may preclude others (including party A) from using composition X according to B's patented use.

What is the U.S. Patent and Trademark Office?

The United States Patent and Trademark Office (PTO) is a noncommercial federal organization governed by the U.S. Department of Commerce. The PTO is staffed with more than 6,000 full-time employees in facilities comprising over 1.4 million square feet in Arlington, Virginia. Established by the U.S. Constitution, the PTO's basic role is to promote the progress of science and technology by temporarily granting inventors an exclusive right to their inventions (in exchange for the inventors' public disclosure of the inventions). Currently, the PTO receives more than 300,000 patent applications per year.

Although noncommercial, the PTO currently operates much like a private business. It provides products and services to customers in exchange for fees, which are, in turn, used to fund all operations. The PTO examines applications and grants patents on properly entitled inventions; it publishes and disseminates patent information; records assignments (ownership) of patents; and maintains search files and a search room of patents that have been issued, available for public use. The PTO also performs similar functions relating to trademarks.

How are patents enforced?

Starting on the date a patent is issued by the U.S. Patent and Trademark Office, a patent gives its owner the right to prevent all others from engaging in a number of activities. The patent grants its owner the right to exclude all others from making, using, selling or offering to sell the invention in the United States, as well as the right to exclude others from importing the invention into the United States. "Infringement" occurs when an unauthorized party makes, uses, sells or offers to sell a patented invention in the United States, when an unauthorized party imports a patented invention into the United States, or when a party induces another party to engage in any of these activities.

Typically the first step a patent owner takes to enforce the patent against an infringing party is simply to inform that party of its infringing acts. This is often accomplished with a warning letter providing the accused infringer with a copy of the patent and informing that party that it is infringing. Very often, the patent owner will also include an offer to license the invention to the infringing party. In many situations, the warning letter and/or the license offer will resolve the situation.

If the infringing party continues to infringe after receiving the warning letter, the patent owner may approach a federal district court to seek legal assistance in enforcing his rights against the infringer. The patent owner may request that the court order the infringing party to stop its infringing acts. Such an order is called an injunction. An injunction may be temporary or permanent. Often along with, or instead of, seeking an injunction, a patent owner files a civil lawsuit in a federal district court accusing the potential infringer of infringing a U.S. patent. All parties take these cases very seriously, as the damaging effects of patent infringement can be extremely large. In the event that a party is found to have infringed a patent, the court will order the infringer to immediately stop its infringing acts and will often award monetary damages to the patent owner to compensate for the infringing acts before and during the trial.

What is a license to a patent?

A patent license is a contract between the owner of a patent and an independent party who wishes to make, use or sell the invention claimed in the patent. Such a contract is in essence a promise by the patent owner that the owner will not sue the independent party, called the licensee, for patent infringement, provided that he or she complies with the terms of the contract. Typically, the licensee agrees to pay the patent owner a percentage of the revenue the licensee receives from sale of the invention and/or other license fees.

Patent licenses are important legal contracts that help to ensure the rapid and efficient utilization of many inventions and the transfer of information for development of future inventions. A patent does not itself ensure that an invention will be used or be economical. Many inventions require significant capital investment before they can be used commercially. This is particularly true of biotechnology inventions, because the cost of developing a drug often exceeds $800 million. By licensing a patented invention to a third party, a patent owner who may not have the resources to fully develop an invention can work with a third party to commercialize it.

In some cases, a license from more than one person may be necessary to use an invention effectively. For example, one party could obtain a patent on a new protein, while a second party obtains a patent on a new use of that same protein. In order to sell that protein for the new use, a third party would require a license from both patent owners. If the two patent owners want to sell the protein for the new use, they would need to grant a license to each other. Such licenses are often called cross-licenses. In rapidly developing fields of technology, cross-licenses are very common.

If a third party does use a patented invention without a license, the patent owner can seek legal remedies for infringement. Such remedies can include damages and an injunction against the infringer to prevent future use.

Why are patents important to investors?

Developing innovative drugs is a risky, time-consuming and expensive process; therefore, companies seek the protection of a patent to ensure that competitors will not immediately copy a product they have researched and developed.

The right that a patent confers to exclude competitors temporarily means that a technically innovative product is more likely to capture a good market and so earn a good rate of return for people who have invested in the company's research. This in turn means the company will be able to conduct further research and advance the state of the art.

Profitability and Patents
A patent does not guarantee that a product will be economically viable and produce any return to investors. Nevertheless, by preventing others from copying a development and thereby undercutting the innovator on price, a patent makes it possible for an innovator to secure a market without having to keep details of its product a trade secret (see "What is the purpose of a patent?"). This makes individual investments more dependable, and it advances technology in general.

On March 14, 2000, stock prices of many biotechnology companies fell sharply after President Bill Clinton and British Prime Minister Tony Blair issued a joint statement that some observers misinterpreted as signaling a change in patent policies. Investors feared that the two countries intended to restrict patents covering gene-based inventions and consequently lowered their valuations of companies that obtain patents on such inventions. In fact, the two leaders' statement signaled no change in patent policies, a point the PTO confirmed later.

How are gene patents different from patents on other chemical structures?

There is no legal distinction between a gene patent and patents on other chemicals. Every gene (including complementary DNA, or cDNA forms) is a molecule that can be defined as a specific chemical structure (see "What is a gene?"). Other molecules that are not genes but have beneficial medical effects have been patented. They too are often defined by their chemical structure. Two examples include:

• Aspirin - a compound whose chemical name is salicylic acid acetate (2-(acetyloxy)benzoic acid). Felix Hoffmann patented it in 1900.
• Beta-Carotene - (U.S. Patent 5,871,766 [1999]) a compound that was defined by its chemical structure.

What questions are at issue in current discussions on PTO policy?

Patents and Human Genes
There has recently been considerable public discussion about the granting of patent rights to human genes. A misunderstanding of the patenting process has generated much of the discussion.

Patents may be granted for human-gene-based inventions if they meet all the standard criteria for a patent. Availability of patent protection for chemical compounds, such as proteins, polypeptides and nucleic acids (including genes), is critical to the success of modern biotechnology. Without strong and effective patent protection, commercial development of new treatments, diagnostic tools, pharmaceuticals and other products would not be possible.

Utility Needed for Patents to Be Granted
Recognizing the critical role of patents in the biotech industry, the PTO has recently issued guidelines concerning the amount of usefulness, or "utility," a prospective patent requires as well as the content of a patent's written description necessary to be awarded a patent. These guidelines allow DNA coding sequences to be patented when the specific function or characteristics of the sequences are described, while denying patents for uncharacterized nucleic acids.

Current Patent Policies
Congress is also keenly aware of the need for contemporary and effective patent policies. In November 1999, Congress amended the patent statute to provide early publication of U.S. applications-18 months after the filing date. This early publication process is similar to that found abroad and will help disseminate new biotech inventions to the public. Additionally, Congress has provided extensions of the patent term beyond 20 years from the filing date to compensate for delays caused by PTO inefficiency, interferences, secrecy orders or appeal processes (see "How long does a patent last?"). These patent-term extensions will greatly benefit the biotech patentee, who often loses valuable patent term due to such delays.

PTO Five-Year Strategic Plan
In June 2002, the PTO released a five-year strategic plan in the hope of increasing patent quality while decreasing patent pendency. To meet these goals, the PTO plans to implement an electronic application-filing system and revise the system of filing fees. The proposed fee system attempts to decrease the burden on PTO examiners by exerting increased fees on longer and more complex patent applications. Currently, the PTO is working with biotech industry leaders to develop a fair fee structure, one that does not place undue burden on high-tech industries, such as biotechnology, that submit more complex patent applications.

What happens when the PTO receives a new patent application?

The PTO first determines that all required parts of an application have been properly submitted. If so, the application is accorded a serial number and filing date and then sent to an examiner with relevant technological expertise. The examiner reviews the application and in due course notifies the applicant (or patent attorney or agent of record) of any action taken. In rare circumstances, this first "Office Action" states that the application will be allowed to issue as a patent. In most cases, however, the first Office Action rejects the application on the basis of lack of novelty, obviousness or noncompliance with other elements of the patent laws, rules and/or guidelines. At this point, the applicant (or the applicant's representative) may respond by stating any perceived errors in the examiner's action and/or amending the application to address the examiner's concerns.

After an Initial Rejection
The cycle of response and rebuttal between examiner and inventor may be repeated, or the examiner may make the rejection final. After a final rejection, the applicant may amend the application to comply with all the examiner's requests, or the applicant may submit an appeal to have the examiner's decision overturned. If the appeal is denied, the rejection remains final and the inventor will not receive a patent without pursuing further litigation. On the other hand, if the appeal is upheld or the examiner determines the application is now in acceptable condition, the application will be allowed to issue into a patent.

The review process may take several years. At some point during examination, it may be deemed that an application is in satisfactory condition. In such cases, a "Notice of Allowance" is sent to the applicant or the applicant's representative. Within three months of the mailing of the Notice of Allowance, an issue fee must be paid for the application to actually issue as a patent, or it will be considered to be abandoned.

How long does a patent last?

Patent terms are usually 20 years from the date on which the application for patent was filed in the United States. This term may be shortened, however, if the inventor filed an earlier patent application on the same invention. In this case, the patent term will be 20 years from the filing date of the earlier application.

Importantly, protection afforded by a patent does not actually start until the patent is granted (i.e., issued). Thus, the enforceable term of a patent is always shorter than 20 years; exactly how much shorter depends on how long the application was examined in the PTO. For example, if an application is examined in the PTO for five years before it is issued, the enforceable patent term will be only 15 years. Examination periods of five years and more are not uncommon. On the other hand, the patent term can be extended for a limited time under certain circumstances (see "What questions are at issue in current discussions on PTO policy?").

Once a patent has expired, anyone may make, use, offer for sale, sell or import the invention without permission of the patentee.

What are the various ways patents are licensed?

An inventor may not have the resources to commercialize an invention. By allowing others to practice under a patent through the use of a license, however, the inventor may allow such inventions to be commercialized, leading to beneficial uses for the public.

The desire of others to practice within certain areas of technology and the licensing of such technology are instrumental in allowing the commercialization of inventions that otherwise might never become available to the public.

Different licenses include the following:

• Royalty-Bearing License - A license that contains terms stating that a licensee agrees to pay the patent owner in incremental payments typically proportioned in some way to the extent of use or revenue the licensee derives from the licensed product.
• Exclusive License - A license that grants the licensee sole right to practice under the patent. However, the exclusive license can be subject to the patent owner's rights or the rights of prior licensees.
• Nonexclusive License - A license that permits more than one licensee to practice under the patented technology.
• Cross-License - When two separately owned patents are required to make, use or sell a product, and both patent owners desire to make, use or sell the product, they each may grant a license to the other, which is referred to as a cross-license.
• Reach-Through License Agreement - An arrangement requiring the payment of a royalty for the sale of a product developed or manufactured through the use of licensed technology.

What is the difference between releasing information into the public domain and patenting it?

Obtaining a patent is just one way of releasing information into the public domain. There are many other ways one can release information into the public domain; for example, one can release information by

• Publishing a manuscript in a peer-reviewed journal.
• Presenting information at a seminar, lecture or interview.
• Submitting a DNA or protein sequence to an electronic public database.

In each example, just as in obtaining a patent, the public receives the benefit of novel information. If information is patented, the inventor does not have the option of withholding the information from the public domain, but the inventor can exclude the public from profiting from the information (making, using or selling the invention).

Patent Publication and the Dissemination of Information
All patent applications filed internationally and most filed in the United States under the new patent act are published 18 months after they are filed, and thus information is quickly released into the public domain.

Patents facilitate academic research, because the release of information to the public is critical to the advancement of knowledge. The fact that an inventor can obtain patent protection on an invention encourages inventors not to withhold beneficial information from the public. In fact, the patent system provides strong incentive for sharing information. Not only can researchers use the information in a patent, but also by disclosing cutting-edge scientific information, the patent system helps prevent expensive duplication of efforts.

What is a patent interference?

Sometimes different inventors file two or more applications claiming essentially the same invention. The patent, however, can be granted to only one of them. In these cases, the PTO instigates a proceeding known as an "interference" to determine who is the actual first inventor and therefore entitled to the patent. Interference proceedings also can be instituted between a pending application and a patent already issued.

In the United States, only the inventor who first made the invention is entitled to obtain a patent. In a patent interference, each party must submit evidence to prove when he or she made the invention. If an inventor cannot submit such evidence, the date of invention is considered to be the date on which the application was filed. A panel of administrative patent judges reviews all the evidence and then decides which party was the first to invent. After a decision by the Board of Patent Appeals and Interferences, the losing party may appeal to the Court of Appeals for the Federal Circuit or file a civil action against the winning party in the appropriate U.S. district court.

How expensive is it to obtain a patent?

Patenting an invention is an expensive endeavor. Almost every step of the process requires a fee. In the United States, an initial filing of a patent application costs about $740 (or more, depending on the number of claims). During prosecution, numerous other fees will be encountered; almost all petitions require a fee, and "extension fees" must be provided any time a document is filed later than requested. Following the notice of allowance, an issue fee of about $1,200 must be paid. At a minimum, these costs will total about $3,000.

Moreover, substantial maintenance fees must also be paid at various intervals during the patent term to keep the patent in force. These expenses, however, do not take into account fees that must be paid to attorneys and agents for performing patent prosecution services, which can increase expenses for obtaining a patent.

There is some relief for individual inventors, small business concerns and nonprofit organizations, as they may file as "small entities" and thus reduce many of the expenses by approximately half.

Currently, the PTO is re-evaluating the structure of fees imposed for patent applications (See "What questions are at issue in current discussions in the PTO?").

Filing patents outside the United States is considerably more expensive than obtaining a U.S. patent. For example, obtaining a patent in Europe may cost more than $100,000.

Which inventors hold the most patents?

Thomas Alva Edison (1847-1931) was awarded 1,093 U.S. patents and thousands more by authorities in dozens of other countries, making him the individual inventor with the largest number of patents. The electric light bulb, the phonograph and the motion-picture camera are merely the most famous of Edison's numerous inventions.

The most prolific individual inventor of recent times was the late Jerome Lemelson, who successfully enforced conceptual patents on the video camcorder and illuminated highway signs, among other things.

Individual inventors have in recent years accounted for about 23 percent of U.S.-issued patents. In contrast, businesses chalk up many more patents. Between 1977 and 1996, General Electric Corp. was the company awarded the most U.S. patents: 16,206.

How many patent applications are filed each year?

The U.S. Patent and Trademark Office currently receives more than 300,000 patent applications each year and expects that number to quadruple by 2006. Universities have been filing increasing numbers of patent applications since the Bayh-Dole Act became law in 1980; they filed more than 4,800 U.S. patent applications in fiscal year 1998.

In 1999, IBM Corp. received the largest number of U.S. patents of any company: 2,756. (IBM also received the most in every year back to 1994.) After IBM in 1999 came NEC Corp. (1,842 patents); Canon K.K. (1,795); Samsung Electronics Co., Ltd. (1,545); Sony Corp. (1,410); Toshiba Corp. (1,200); Fujitsu Ltd. (1,192); Motorola Inc. (1,192); Lucent Technologies (1,152); and Mitsubishi Denki K.K. (1,054). The U.S. government received the largest number of U.S. patents of any organization in 1993, but by 1998 its annual total of 1,017 patents left it outside the top 10 patent-receiving organizations.

Do public institutions hold patents?

Many public institutions and government agencies have obtained and continue to apply for and obtain patents. For example, the following numbers of patents were granted to these leading universities between 1969 and 2000, according to the PTO:

• University of California, The Regents of - 3,203 patents
• Massachusetts Institute of Technology - 2,264 patents
• Stanford University - 1,064 patents
• California Institute of Technology - 955 patents

These patents cover a wide range of discoveries, such as novel compositions (e.g., pharmaceuticals), methods of conducting research, methods of treating and diagnosing disease and methods of improving agriculture. They also include design patents (e.g., architectural designs, mechanical designs and textiles). In the biotechnology area, one key patent held by Stanford University (the "Cohen-Boyer patent") covered until its expiration the basic method of making recombinant DNA; any commercial entity using recombinant DNA was required to obtain a license from Stanford and to pay the university annual fees plus a royalty on the sales of any product developed using the recombinant technology.

Government Filings
Government agencies also file for and obtain patents. For example, the Department of Health and Human Services, which includes the National Institutes of Health, has obtained over 1,200 patents. These patents cover a wide range of discoveries affecting the quality of human health, including methods of detection and treatment of disease, methods of conducting scientific research, individual genes and proteins, and the use of such genes and proteins.

What's the difference between the Human Genome Project and private sector genomics research?

The Human Genome Project
The Human Genome Project (HGP) is an international endeavor coordinated by the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH) through the National Human Genome Research Institute. The project formally started in 1990 and was expected to take 15 years to complete.

The main objective of the HGP was to sequence and map all human genes, a project that will be finished in 2003-two years ahead of the original schedule. With the completion of this project, the mission of the National Human Genome Research Institute is expanding to include studies of how the human genome functions to create proteins.

Private Research
In contrast to the HGP, individual investors finance private-sector genomics research. The goals of private sector genomics research typically overlap and extend those of the HGP. While private sector genomics companies also aim to identify all (or most) of the genes in human DNA, these companies further seek to use this information as a starting point for development of therapeutically useful compounds and disease treatment strategies.

Interestingly, competition by private sector companies in the genomics arena spurred the federally funded HGP to quicken its pace to achieve its objective before the original year 2005 deadline. In February 2001, the HGP along with Celera Genomics published details of a completed working draft of the human genome in the journals Science (2/16/01) and Nature (2/15/01). The complete "polished" version is slated for publication April 2003.

How many patents has the PTO issued covering gene sequences?

The PTO has issued far fewer patents encompassing gene sequences than it has patents on inventions in the fields of electronics, telecommunications, medical devices and advanced materials. As of the end of 2001, the PTO had issued over 6,500 patents covering gene and open reading frame sequences (DNA sequences that code for proteins). Of these, over 1,300 patents were for human genes or open reading frames. To date more than 20,000 applications for genes, DNA fragments, SNPs and so forth have been submitted for review.

Major holders of gene-based patents as of year-end 1999 were

U.S. Government	388 patents
Incyte Pharmaceuticals	356 patents
University of California	265 patents
SmithKline Beecham	197 patents
Genentech	175 patents
Eli Lilly	145 patents
Novo Nordisk	142 patents
Chiron	129 patents
American Home Products	117 patents
Isis Pharmaceuticals	108 patents
Massachusetts General Hospital	108 patents
Human Genome Sciences	104 patents
University of Texas	103 patents
Institut Pasteur	101 patents

U.S. inventors predominate as recipients of U.S. patents in genetic engineering. Other countries with a strong patent showing in the field are Japan, the United Kingdom and Germany.

What are the attitudes held by religious leaders toward gene patents?

Few religions have given specific consideration to patents that cover gene-based inventions.

A religious coalition assembled in 1995 called the Joint Appeal Against Human and Animal Patenting, gained press attention by expressing opposition in general terms to patents covering living things as well as genes. The Joint Appeal did not, however, reflect a consensus among religions, or even among the religions represented. Most of the religious leaders who participated were not representing official positions, and many theologians have criticized the group's anti-patent statement. The U.S. Catholic Conference declined to support the statement.

Subsequently, the American Association for the Advancement of Science conducted a Dialogue Group on Genetic Patenting that included representatives from a variety of religions. This group adopted a more cautious view. It was opposed to patents on genomic DNA sequences, that is, on genes as they exist in the chromosomes. The group did not take a position on the patentability of inventions that include gene sequences. At least one theologian in the dialogue group found no religious objection to patents on such inventions.

More information on this topic can be found in Unprecedented Choices: Religious Ethics at the Frontiers of Genetic Science, by Audrey R. Chapman (Fortress Press, Minneapolis, 1999).

What are some of the great patent fights?

One of the largest patent battles in U.S. history resulted when Polaroid sued Eastman Kodak for infringement of its patents covering instant photography cameras. In 1990 Polaroid secured a $925 million judgment against Eastman Kodak.

Biotechnology is not immune to patent disputes. Two major patent court cases involved erythropoietin (EPO) and an enzyme, taq polymerase, used in a widely employed analytical technique. The first case, concluded in 1996, involved Amgen and Genetics Institute. The court ruled that Genetics Institute could not sell its version of EPO in the United States, giving Amgen a legal monopoly over the sale of EPO to kidney dialysis patients. The second case involved Hoffmann-La Roche and Promega Corporation. In this case which is still under appeal at the writing of this document, the court invalidated a patent covering taq polymerase, which is used in the polymerase chain reaction method of amplifying DNA.

Most disputes about patent claims are settled amicably with licensing or cross-licensing agreements. Companies generally prefer to avoid the expense and time that litigation entails.

What is an EST?

An EST, or "expressed sequence tag," is a DNA sequence of several hundred nucleotides. As the name implies, an EST is DNA that codes for a particular protein. ESTs are DNAs that have been transcribed and are ready to be translated into a protein. An EST is typically obtained by determining the sequence of several hundred nucleotides of one end of a gene. Because several hundred nucleotides are more than sufficient to distinguish any given gene from all other genes, an EST is a convenient means of identifying a specific gene in the context of a single chromosome, a complete genome or a collection of genes (often called a "library").

EST Uses
ESTs have a number of immediately useful characteristics. For example, an EST can be used as a label to map a specific location on a chromosome. Because the sequence information contained in an EST is enough to distinguish one gene from all others, each EST may be used to identify the chromosomal location of its corresponding gene. The ability to identify where a particular gene is on the chromosome is important in the detection of chromosomal mutations and corresponding disease states. Using an EST as a tool in this way may allow a doctor to diagnose a particular genetic disease in time to provide a preventive treatment.

ESTs may also be used to distinguish between cell or tissue types. Although nearly all cells and tissues of a given organism contain all the genes of that organism, each cell or tissue type typically expresses, or manufactures, the proteins encoded by only a subset of genes (for example, a gene involved in vision may be expressed by a retinal cell, but not expressed by a muscle cell). Thus, because each EST corresponds only to a single expressed gene, a scientist or doctor may use an EST to identify a cell or tissue by which gene or genes are expressed or not expressed. In a similar way, ESTs may also be used as molecular tools in criminal investigations.

EST Patents
Currently, many patent applications directed to ESTs are pending before the U.S. Patent and Trademark Office. The PTO has adopted the policy that an EST may be patented if it meets the utility, novelty and the nonobviousness requirements.

Does a U.S. patent protect a company in other parts of the world?

No, a patent in the United States affects only activities that occur in the United States. If an inventor wishes to protect an invention in another country, a patent application must be submitted in that country and a patent obtained.

To simplify this process, most major industrialized countries have adopted the Patent Cooperation Treaty (PCT), which allows an inventor to file a single application simultaneously in each of a large number of countries. This "international," or PCT, patent application has the effect of a national patent application in each country that is designated in an application. The international patent application must be prepared in accordance with international standards effective in all PCT contracting states. Although the PCT permits an inventor initially to file a single application internationally, eventually the inventor must, through the PCT process, obtain a patent in each country for which protection is sought.

International Patent-Awarding Processes
Unlike in the United States, in foreign countries a patent is awarded to the inventor who first files a patent application, not necessarily to the person or organization that invented an invention. Thus, the international patent system imposes a significant incentive for an inventor to file as early as possible.

U.S. citizens and companies file patent applications internationally, and also a large number of foreign nationals likewise file applications in the United States. For example, from 1996 to 1998, residents of foreign countries filed more than 43 percent of all U.S. patent applications.

Are academic researchers exempt from the patent laws?

There are very few exemptions from the patent law. One of those is the research exemption, which protects scientists who are engaging in "philosophical" research. The overriding goal of providing an inventor exclusive rights is to provide the public with new and useful inventions and the associated knowledge; issuing a patent gives the inventor an incentive to fully disclose his invention and related information. However, the patentee's rights must yield when the benefit to the public outweighs the harm to the patentee.

The judicially created research-use doctrine is a recognized limitation on the patentee's right to exclude others from making, using or selling the invention in the United States during the patent term. This doctrine holds that it is not an act of infringement to make and use a patented invention if the use is limited to research or experimentation and the user (or institution) does not profit or gain any advantage in its business from the research.

The courts have interpreted this doctrine narrowly. Courts have held that the research exemption does not apply if the scientist conducts experiments to adapt the patented invention to further any commercial or "business" interests. However, academic researchers may be outside the scope of the exemption if their activities further the interests of their institutions, such as in attracting researchers or securing research grants. In practice, the effective standard is pragmatic. With rare exception, a patent owner will not go to the trouble and expense of infringement litigation if the research activities in question do not implicate its commercial interests.

Some proponents of broadening the exemption do not want the test to be based on whether the use of the patented invention was "for profit" and, therefore, infringing. Rather, they believe that the exemption should allow the patented invention to be used by any party to develop an improved product or another product.

Research-Exemption Legislation
Congress has enacted laws for two specific research-use exceptions to liability for infringing intellectual property rights, one involving the patent statute, and the other, the Plant Variety Protection Act ("PVPA)

The first permits basic research on a pharmaceutical invention during the life of a patent if the research is to develop and submit information to the FDA. It appears in the patent statute at 35 U.S.C. section 271(e)and was enacted as part of the Drug Price Competition and Patent Term Restoration Act of 1984 (the "Hatch-Waxman" Act). This statute provides for a limited research-use exemption for the use of a patented invention "solely for uses reasonably related to the development and submission of information" for FDA approval. While a patented drug cannot be placed on the market (and profit derived therefrom) by another during the life of the patent without infringing, basic research and clinical validation can be performed to develop and submit information to the FDA during the life of the patent. Section 271(e)(1) protects both studies involving a drug that would not infringe the patent and studies to support a generic version of the patented drug for approval when the patent expires.

The other statutory research exception broadly permits the use and reproduction of a protected plant variety for plant breeding or other bona fide research. It is found in the PVPA (7 U.S.C. section 2321 et seq.). Section 2544 provides that "[t]he use and reproduction of a protected variety for plant breeding or other bona fide research shall not constitute an infringement of the protection provided under this Act" (i.e., it immunizes the user from liability under the PVPA) The PVPA was enacted to encourage the development of novel varieties of sexually reproduced plants and to make them available to the public, thus providing protection to those who breed, develop or discover them, and thereby promoting progress in agriculture in the public interest.

What international treaties or establishments have been created to protect inventors?

Uruguay Round General Agreement on Tariffs and Trade (GATT)
On December 8, 1994, President Clinton signed the "Uruguay Round Agreements Act" (URAA). The URAA implements the Uruguay Round General Agreement on Tariffs and Trade (GATT), which includes an agreement on the Trade-Related Aspects of Intellectual Property. This sets out the minimum standards of protection for intellectual property to be provided by each party to the agreement. Each of the main elements of protection is defined, namely, the subject matter to be protected, the rights to be conferred and permissible exceptions, and the minimum duration of protection. The agreement requires that members comply with the main conventions of the World Intellectual Property Organization, a United Nations agency that promotes the protection of intellectual property.

The Uruguay Round Agreements Act also set a term for all patents in force or filed as of June 8, 1995, of 17 years from the date the patent was granted, or 20 years from the date of the first filing of the patent application, whichever is longer. All patents filed after June 8, 1995, will have a patent expiration date of 20 years from the date of first filing of the patent application.

The Trilateral Offices
In addition to the GATT agreement, the United States, Europe and Japan are working to harmonize their patent systems through the establishment of the Trilateral Offices. The Trilateral Offices-the European Patent Office (EPO), the Japanese Patent Office (JPO) and the U.S. Patent and Trademark Office (PTO)-have since 1983 been cooperating on the administration of their patent functions.

One of the activities of the Trilateral Offices is to exchange information and views regarding patent administration in general, patent documentation and classification, automation programs and patent examination practices. Advantages of this institutional cooperation include reduced costs, better patent quality, reduced processing time and improved information dissemination.

For the past 15 years, a Trilateral Conference has been held annually, and the results have been contributing to mutual agreements and developments in the field of patent systems.

The World Intellectual Property Organization (WIPO)
The World Intellectual Property Organization (WIPO) is a specialized U.N. agency that promotes the protection of man-made creations for the economic, social and intellectual advancement of all people. WIPO aims to help disseminate intellectual property information between nations, harmonize the systems by which these nations review and protect property rights, and assist in resolving related international disputes. Centrally located in Geneva, the WIPO is supported by 179 member states and currently oversees 23 treaties that protect intellectual property.

WIPO plays a vital role in the harmonization of intellectual property laws internationally by maintaining the Patent Cooperation Treaty (PCT.) The patent system this treaty established allows an inventor of one member state to file a single patent application for any or all nations that have adopted the PCT as long as the application fulfills the requirements outlined in the treaty. Currently, more than 110 nations are members of the PCT Union. This multinational agreement streamlines the process by which an inventor gains the property rights that protect an invention globally.

The history of WIPO dates back to the Paris (1883) and Berne conventions (1886) when separate International Bureaus were established to administer their respective treaties. The Paris Convention sought to protect patents, trademarks and industrial designs, while the Berne Convention was adopted for the protection of artistic endeavors (visual arts, literary works, music, etc.). The two international secretariats that emerged from these conventions were combined in 1893 to create BIRPI, the precursor to WIPO (BIRPI is an acronym for the French translation of "United International Bureau for the Protection of Intellectual Property").

In 1960 BIRPI moved from Berne to Geneva to be closer to the United Nations and was replaced seven years later by the WIPO. At that point, all multilateral treaties were reformed so that oversight was transferred from the Swiss government to the WIPO's member states. During this time, the organization underwent administrative and structural changes, and on December 17, 1974, the WIPO became a specialized U.N. agency. As such, the WIPO is now an independent member of the United Nations that retains its own governing body, budget, constitution and staff, with an obligation to act upon the intellectual property concerns of the U.N.'s member states.

What is genetic testing?

A variety of tests now makes it possible to examine a person's DNA to determine the sequence of the nucleotide bases at critical points within genes that, when mutated, can cause disease (see "How will the discovery of new genes help society?"). The DNA is typically obtained from a blood sample.

Certain DNA sequences have been shown to cause disease or increase the risk that a healthy person will develop a disease later in life. Genetic tests provide physicians with information about the DNA sequence of a particular gene for a particular person. With this information, a physician can prescribe drugs, special monitoring, or preventive measures to treat the disease or reduce the risk that it will develop. This is the subject of a new area of medicine called pharmacogenomics. Some people with an inherited predisposition to a type of colon cancer owe their lives to genetic testing. The test results prompted physicians to remove part of the colon before it turned cancerous.

Some genetic tests can detect whether someone may be a carrier of a genetic disease, even though neither parent is affected. If two carriers of the same disease have a baby, the baby may inherit the condition.

Some forms of genetic testing have already achieved wide acceptance: for example, many people of Jewish ancestry as well as French Canadians choose genetic testing to learn whether they are carriers of Tay-Sachs disease, a lethal condition, because the disease, though rare, occurs more frequently in these groups than it does the general population. Some people prefer not to have genetic tests that may indicate a tendency to develop illness, however, especially if there are no therapies to prevent or delay the condition.

As medical science advances, more genetic tests are likely to become available, and these will likely indicate tendencies to develop diseases not normally thought of as "genetic": diabetes, for example. Tests based on single-nucleotide polymorphisms (SNPs)-tiny but common genetic variations in DNA sequences-could fall into this category.

How useful are genetic tests?

In some cases, the results of a genetic test confirm a physician's suspicion that the cause of a patient's symptoms is an alteration in the normal DNA sequence for a particular gene. Increasingly, this information can indicate to the physician what type of treatment may be best. Many diseases, however, are not caused by changes in a person's DNA sequence. Moreover, genetic tests cannot detect all changes in DNA that do cause disease. Some of the rarer genetic changes that cause cystic fibrosis, for example, are not detected by current tests.

Detected alterations in a DNA sequence in some cases may produce disease but do not always do so. For example, there are people with the gene alteration often responsible for fragile-X syndrome who exhibit few or none of the symptoms typical of that disease. Genetic tests, although they can often help physicians, are merely one more type of medical information. A test on the protein encoded by a gene, rather than on the gene itself, may yield the same information.

Genetic tests that can predict a likelihood of illness generally do not do so with certainty. Rather, they indicate an elevated risk of disease, much as a high cholesterol count indicates an elevated risk of heart problems. As science advances, it is likely that more tests will be developed that indicate some statistical propensity toward disease in later life.

What is the basis for fearing genetic discrimination?

Although genetic tests provide valuable, and often lifesaving medical information, some people fear that if the result of a genetic test indicates that they have either a genetic disease or an increased risk of developing a disease, employers, insurance carriers, schools and others may discriminate against them. This is one reason some people prefer not to take tests that may indicate they could develop a serious disease, especially if there are currently no effective preventive measures or treatments.

One concern is that insurance companies or employers might deny life or health insurance coverage or charge higher rates for people who are at risk for a genetic illness. The insurance industry, however, argues that it must have access to the same information on individual policyholders that the policyholders themselves can access. Decisions about insurability are based on a variety of types of medical information, such as previous diagnoses.

Genetic Discrimination Protection
Some 40 states have enacted anti-discrimination legislation that addresses the use of genetic information by insurers (as of June 2001), and 29 states have legislation protecting employees from genetic discrimination (as of May 2001). Also, on February 8, 2000, President Clinton banned discrimination in the federal workplace based on genetic information.

The Americans with Disabilities Act offers protection from employment discrimination to individuals affected by a genetic condition or disease, and to individuals who are regarded as having a disability. The Federal Health Insurance Portability and Accountability Act of 1996 provides protections against discrimination in health insurance by limiting pre-existing condition exclusions. It also prohibits discrimination against individuals based on health status, including their genetic information.

The Biotechnology Industry Organization has long advocated legal protections to prevent genetic discrimination against individuals.

What is gene therapy?

Gene therapy holds major promise for medical science to correct genetic defects by replacing, augmenting or eliminating absent or defective genes, as well as by providing genes encoding therapeutic or immunogenic proteins.

Gene therapy could potentially be used to combat inherited disorders, such as hemophilia; disorders requiring enhanced production of a protein, such as critical limb ischemia; or acquired diseases such as cancer, cardiovascular disease and HIV infection.

One method of gene therapy works by replacing a patient's ineffective or absent gene with a therapeutic gene (i.e. a replacement gene). The therapeutic gene enables the patient's cells to produce a specific protein that prevents or fights a disease or disorder.

Because the new protein is produced in the patient's own cells, it is recognized as "self."

Gene therapy requires that the therapeutic gene be delivered into the cell. The vehicles for this delivery are called vectors. The most effective vectors come from simple viruses and DNA plasmids, which can penetrate the cell and deliver the therapeutic gene.

As genetic research moves ahead, gene therapy will provide researchers and patients with the ability to combat a wide range of diseases and disorders.

How can genetic confidentiality be ensured?

Because of public concern about potential discriminatory misuse of medical information, BIO supports federal legislation to protect the confidentiality of individuals' medical information, including the results of genetic tests. BIO believes that information resulting from clinical genetic testing and genetic research must be treated responsibly and safeguarded from discriminatory misuse. Federal legislation would standardize protections across the country and thus avoid the difficulties posed by the emergence of a patchwork of different state laws.

Although patients' rights must be protected, it is also important to ensure that regulations or laws do not prevent medical researchers from sharing data from which patient-identifying details have been stripped. BIO opposes further restrictions on the use of encoded data that provide no threat to patient confidentiality

Because genetic tests are a type of medical test, BIO believes they should not be regulated differently from other medical tests. The Clinical Laboratory Improvement Amendments of 1988 provide a regulatory system that oversees all laboratories performing clinical testing. BIO believes this existing system can be adapted to provide appropriate protection of patients' genetic and other medical information.

What have our nation's greatest minds thought about patents?

Thomas Jefferson: "The issue of patents for new discoveries has given a spring to invention beyond my conception."

Abraham Lincoln: "The Patent System added the fuel of interest to the fire of genius."

President Dwight Eisenhower: "This system has for years encouraged the imaginative to dream and to experiment in garages and sheds, in great universities and corporate laboratories. Innovations and discoveries have created new industries, giving more and more Americans better jobs and adding greatly to the prosperity and well-being of all."

Mark Twain: "A country without a patent office and good patent laws was just a crab and couldn't travel anyway but sideways or backwards."

Thomas Alva Edison: "Verily a pioneer has to get his justice in the same way that a florist gets bouquets from century plants." Supreme Court Justice Felix Frankfurter: "The average person reaps the benefits of this form of property because the inventor has created it under a patent system that rewards the inventor ONLY if society DOES derive benefit from it."

Where can I get more information?

The following Web sites offer interesting information about patents:

Biotechnology Industry Organization	www.bio.org
U.S. Patent and Trademark Office	www.uspto.gov
Intellectual Property Owners Association	www.ipo.org
Franklin Pierce Intellectual Property Mall	www.ipmall.fplc.edu
IBM Intellectual Property Network	www.patents.ibm.com
Science and Technology Indicators	www.nsf.gov/sbe/srs/seind98/access/c6/c6i.htm
The Biojudiciary Project	www.biojudiciary.org