Gene patenting

Dear Aanya,

Please do not confuse Indian and US patent laws. US laws are much more developed than Indian law and takes care of most implications that may arise however the issue of gene patents is debatable even in US. First of all you should know that only genes which are isolated from humans i.e. isolated DNA are patentable in US. Secondly,  I suggest you study the case of Myriad Genetics for BRCA1 and BRCA2 genes which related to breast cancer genes. The position since the referenced article was written has changed and in 2010 a US federal court invalidated Myriad's gene patents since he considered even isolated DNA to be product of nature. Even the method of isolating the gene was not allowed by the court under 35 USC 101. The case is under appeal and the US position will be clear in due course. Hampering of research by scientist was one of the arguments raised against Myriad while they claimed that they have allowed scientists to freely use BRCA genes for research.

The position in India is again unclear in absence of any court decision but my understanding from the Act itself is that gene patents would come under the ambit of non-patentable subject matter since they may be considered to be against morality and public order, they occur in nature and they may be considered mere discoveries. 

Hope this helps.

Abhinav Bhalla

Advocate l Registered Patent Agent

abhinav@brbhallaassociates.com

Dear Aanya & Abhinav,

Couple of my observations.

As Abhinav pointed out the news article you pointed out is very old. However there are equally strong arguments from those wanting to have so called “gene patents” (the word gene patent has been a highly abused word, without really understanding what it actually is) and those opposing them. It will be a long debate when we start arguing whether the so called gene patents (which in fact are isolated DNA sequences, allegedly a “lawyers trick”) should be a patentable subject matter or not. In my view, as the law stands in many of the major jurisdictions presently, they are patentable subject matter, including INDIA (they do not come under non-patentable subject matter under the Indian Patent Act).

I would request you to do some investigation. Do a Google search and you will find out how both sides present their arguments. This will help you understand and appreciate the concerns of each side. I would also urge you to read the recent decision of federal circuit related to BRCA gene patents delivered in July 2011. It has upheld the validity of patents related to isolated DNA sequences. The battle is going to continue further.

“Nobody else can test for it” – indeed YES, if they are testing it commercially………any kind of testing for research purpose is not considered infringing. If someone considers this as infringing, I can only pity his/her understanding of patent laws. BTW, I am in favour of the so called gene patents!

·         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 which forms the base of each DNA molecule. There are four kinds of nucleotides in the Human body, namely- deoxyadenosine (A), deoxyguanosine (G), deoxythymidine (T), and deoxycytidine (C). It is the “permutations and combinations” order of these individual “bases” that result in the double helix of the DNA 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 known as the cell. Organisms from single-celled protozoan 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 provides an organism with its own unique traits.

The question that arises, then, is what is gene patenting? "Gene patenting" is a broad term referring to the patenting of either a process that involves isolation of DNA (where DNA refers to either DNA or associated materials such as RNA) as well as to a chemical substance related to DNA. A patent is not received on just a gene. A patent is received on a gene, gene sequence, or gene fragment based inventions. DNA products usually become patentable when they have been isolated, purified, or modified to produce a unique form not found in nature. Isolated and purified genes are patentable inventions if they meet the Patent and Trademark Office's standard criteria, including being novel, well described and useful. Patents are granted on "isolated" genes and gene products where the gene or gene product has real world applicability The patents cover genes and gene products that could be obtained from any person, for example from a blood sample. Gene-based patents have helped to secure the biotechnology and pharmaceutical industry's interests in the development of gene-based therapeutics. For example, the gene encoding erythropoietin was cloned in 1985, which lead to the production of recombinant EPO (Rhu-EPO). This gene was patented by Amgen in 1987 . The protein expressed by this gene is used in the treatment of anemia arising from several disease conditions. A 'genome', on the other hand, is the complete set of genetic instructions carried within a single cell of an organism. A gene is a small subunit of the genome which in general ‘codes for’ - contains the information necessary for constructing - a single protein, or protein subunit. The human genome is estimated to comprise more than 120,000 genes.

·         Expressed Sequence Tag

An EST, or "expressed sequence tag," is a DNA sequence of several hundred nucleotides. As the name implies, ESTs are DNAs that code 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 termed a "library"). 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 on a chromosome. The ability to identify the chromosomal location of a particular gene is important in the detection of chromosomal mutations and corresponding diseases. Using an EST as a tool in this way may allow a doctor to diagnose a particular genetic disease in time to provide an effective preventive treatment. ESTs may also be used to distinguish between cell or tissue types.

·         Genetic Testing

A variety of tests now make it possible to examine a person's DNA to determine the sequence of the nucleotide bases at critical points within a particular gene. The DNA is typically obtained from a blood sample. Certain DNA sequences have been shown to cause disease or to confer an increased 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 people prefer not to have genetic tests that may indicate a tendency to develop illness, however, especially if there are at present 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.

·         Gene Therapy

Gene therapy holds major promise for medical science to correct genetic defects. This can be achieved 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 diseases and HIV infection. One method of gene therapy works by replacing a patient's ineffective or absent gene with a therapeutic gene (e.g. 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 processed with a precision required by the patient's body, and is recognized as "self." Gene therapy requires delivery of the therapeutic gene into the cell, utilizing vectors. The most effective vectors come from simple viruses and DNA plasmids, which can effectively penetrate the cell and deliver the therapeutic gene. As genetic research moves into the future, gene therapy will provide researchers, and patients, with the ability to combat a wide range of diseases and disorders.

·         Definition and Requirements of a Gene 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. 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. A patent grants exclusive rights to inventors for limited periods of time.

Under Section 101 of the U.S. Patents Act, 1957, 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 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 inventions generally fall into one of two different classes:

·         One class is 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.

·         The second class of biotechnology inventions includes 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.

In order to obtain a gene patent, an inventor must show that these four criteria are met:

·         The invention must form patentable subject matter. According to the “product of nature” theory, “any kind of structure made by a human hand” is patentable, but things that exist in substantially the same form in nature (that is, not made by human hand), namely “products of nature” are not patentable. 

The position in law vis-à-vis separation using recombinant DNA technology is when the human and material resources inserted in research reach a certain level, the product of such research is protected under patent law. Judge Hand’s opinion in the case of Parke-Davis & Co. v. H.K. Mulford  & Co  illustrates that patents are not denied merely because products of nature are claimed. This suggests that if there is sufficient reason for granting a patent, then the subject-matter requirement will be satisfied even if the subject matter claims product of nature. It has been said that the difference between a discovery and invention is a difference in degree rather than kind.

It was held in the well-known case of Diamond v. Chakraborty by the United States Supreme Court that genetically manipulated organisms are subject matter under section 101. In light of the “product of nature” theory, the Court’s reasoning can be comprehended, as there was no corresponding organism to the claimed organism in nature. The Court further said in this case that statutory subject matter includes “anything under the sun made by man”.

A patent claim over an isolated and purified DNA molecule could cover either a gene excised from a natural chromosome or a synthesized DNA molecule. In response to objections received by the United States Patent and Trademark Office regarding patentability of “isolated and purified” DNA molecules, it said that an isolated and purified DNA molecule that has the same sequence as a naturally occurring gene is eligible for a patent because (1) an excised gene is eligible for a patent as a composition of matter or as an article of manufacture because that DNA molecule does not occur in that isolated form in nature, and (2) synthetic DNA preparations are eligible for patents because their purified state is different from the naturally occurring compound.

The position in the European Union Directive on the Legal Protection of Biotechnological Inventions, 1998 is given under Article 5 and is as follows-

1.  The human body, at the various stages of its formation and development, and the simple discovery^] of one of its elements, including the sequence of a partial gene, cannot constitute a patentable invention.

2.   An element isolated from the human body or otherwise produced by means of a technical process, including the structure or partial structure of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element.

·         The invention must be novel and non-obvious. 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 non-obviousness usually means that the inventor must have newly discovered the chemical structure of the gene or protein. If that structure already is known, the inventor cannot meet this requirement. The requirement that the claimed subject matter be "new" is an integral and historically constant feature of U.S. patent law. Traditionally, courts have interpreted the requirement of newness as excluding from patentable subject matter certain discoveries that lack invention, such as laws of nature[13] and, most importantly for purposes of the subject at hand, naturally occurring products, processes, and other phenomena. The non patentability of these categories was established under the 1952 Act as well as under its predecessors. Thus, a plant, animal, or microbe newly found in the wild, or a mineral or chemical newly discovered in the earth, or any part of a plant, animal, microbe, mineral, or chemical is not patentable subject matter; such discoveries are "manifestations of nature, free to all men and reserved exclusively to none."[14] "Novelty," defined in section 102 is satisfied by a showing that the claimed product or process was not previously known or used by any other person in the United States. In addition, the invention must not have been patented or described in a printed publication in the United States or a foreign country, or in public use or on sale in the United States more than one year prior to the application date. The "non obviousness" criterion, defined in Section 103 was added to the 1952 Act and requires that the product or process not be self- evident to a person having ordinary skill in the relevant arts. This does not mean that the non-obviousness requirement for a product patent may be satisfied by the non-obvious method by which the claimed invention was discovered. Rather, it means that the claimed invention itself would not be obvious to a practitioner. If the invention itself is obvious, it does not matter whether the method of discovery is non-obvious. Similarly, if the invention itself is non-obvious, whether or not the process by which it was discovered was well known is irrelevant. Put differently, if the patent sought is a process patent, then the process must be non-obvious, and the non-obviousness of the product made by the process is inconsequential. If what is sought is a patent on a biochemical, then the molecule must be non-obvious.

·         The invention must be useful. The inventor must show that the invention has a real-world use. It is not 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. In early U.S. case law, only minimum utility was required. Prior to Brenner v. Manson , inventions were useful if capable of some beneficial use to society. The aforementioned case changed this view and required `substantial utility` and `specific benefit...in currently available form`. Thus, Brenner established the view that a compound which is only useful in research does not meet the utility requirement, even if that research could lead to a useful product. Thus, the test of utility refers not to commercial viability, but to the necessity that the invention be put into practice. The United States Patent and Trademark Office has issued utility guidelines. aimed at stopping companies from making frivolous attempts to patent genes before they have established a particular use for them. The rules are intended to help end a bitter debate on gene patenting. These regulations have put to rest any question about whether genes can be patented at all -- making it clear that companies may indeed patent both whole genes as well as pieces of genes, though genetic sequences or ESTs are not patentable. The new guidelines have placed a more stringent utility requirement. To demonstrate utility as that term is now interpreted by the Patent and Trademark Office of the United States, the applicant must show a specific, substantial, and credible use for the claimed invention. This may curb many companies from racing to file a patent immediately after isolating the DNA or gene as a specific and substantial use must also accompany the application.