BIOTECH PATENTING 101
 

by Warren Kaplan

The Patent System

A United States patent is essentially a contract between the U.S. government and the inventor that has its roots in Article 1 of the U.S. Constitution. In exchange for allowing the invention to be put into the public domain, the government allows the inventor to exclude other people from developing the patented method or product for a limited period of time. Specifically, this exclusionary right extends to making, selling, using, offering for sale, or importing the invention that is the subject of the patent. For most inventions dealing with biotechnology, the exclusionary right ends twenty years after the date that the application for the patent was filed. After this exclusionary period is over, the invention can be freely used by anyone.

Specifically, what the inventor gets to exclude is the use of the invention as defined by the patent “claims,” which are described in detail in numbered paragraphs at the end of any issued patent. Just as the deed to a house describes the physical property of the homeowner (i.e., one hundred feet Northwest to X street, two hundred feet East to the big tree....), the claims in a patent application define the intellectual property of the inventor. The “claims” determine how broad (or narrow) the inventor’s exclusionary power is, and also set infringement limits for public use of the invention.

Patents on Genes

Not all inventions are patentable. The U.S. Patent Office requires the inventor to show three things about the invention before it can be patented. The invention must be “novel,” “non-obvious,” and “useful.”

In 1980, in Diamond v. Chakrabarty, the United States Supreme Court held that patent law does not distinguish between “living and inanimate things..." but does distinguish between " products of nature, whether living or not, and human-made inventions.” It has been generally agreed that the Chakrabarty case opened the floodgates to the suite of biotechnology-related subject matter now available for patenting. Whether or not one agrees that patenting DNA or genetically modified animals and tissues is a benign act, it is important to understand the legal underpinning supporting this dazzling (to some) array of innovation.

The Chakrabarty patent was not the first U.S. patent directed to recombinant DNA technology, nor was it the first U.S. patent on a living creature. Chakrabarty was, however, best known for its language asserting that in principle, “anything under the sun that is made by man” may be patentable if it meets the Patent Office’s legal requirements. Table 1 is a summary of examples of the kinds of patents issued by the U.S. Patent Office around the time of this ruling. The Chakrabarty decision was the culmination of several different legal tracks.

First, the general ability to get a patent on a living organism dates back to the remarkable patent issued to Louis Pasteur in 1873. Pasteur obtained a patent on a process/apparatus for making beer and to a purified yeast cell (Table 1).

Second, it is well settled patent law that methods or processes are patentable subject matter. Chakrabarty actually applied for two patents-one on the method of using organisms to degrade oil, and one on the organisms themselves. The patent application on the method caused no stir at the Patent Office and it took just two years to get this patent issued. The Patent Office had more of a problem with the second Chakrabarty patent application on the actual organism. Some other patent applications on biotechnology methods also have taken several years. For example, the Cohen and Boyer patent on basic cloning methodology took six years to issue. The second, and key Chakrabarty patent, however, on a composition of genetically modified bacteria (U.S. 4,259,444) took nine years to work its way through the Patent Office. Once Chakrabarty II was issued, however, others quickly followed such as the patent to an “essentially pure” plasmid (U.S. 4,273,875). This plasmid patent took only two years to pass through the Patent Office and it’s probably the first real DNA patent since the plasmid was nothing more than a circular DNA sequence. It was issued soon after Chakrabarty II. The first true “gene” patent may well be U.S. 4,322,499 (see Table) and the first patent on a therapeutically important DNA was probably the U.S. 4,530,901 patent on alpha interferon.

Third, there is a line of case law that says the mere “discovery” of some product is not proper subject matter for patent protection unless the product was created by the discoverer (i.e., is manmade). In American Fruit Growers, Inc., v. Brogdex Co. in 1931, the court held that a patent on a fruit whose skin is impregnated with a chemical compound is not patentable since the fruit is not transformed into a new and different name, character, or use.

Fourth, a known biological material is patentable if it is in a purified or concentrated form and therefore not previously described, i.e., the so-called “purity” line of cases emanating from the U.S. Patent Office. This idea was stated in 1970 in the In re Bergstrom case, where the court said pure materials are by definition novel as compared to impure materials. Thus, one can get a U.S. patent to a “biologically pure” mold (Streptosporangia sp.) and there are plenty of other examples.

Patents in Practice

How do these various legal threads come together in practice? Imagine this most simple of hypotheticals. You are a patent lawyer for a biotechnology company. A scientist clones gene X, which encodes the cell-surface receptor for soluble protein Y. The gene sequence X is not in any database. Protein Y binds to its receptor, inducing inhibition of nerve growth. Thus, gene X might be used to make a soluble receptor to “soak up” protein Y and antagonize its function- therefore allowing nerves to grow. There is a huge commercial market in treating spinal cord injury and peripheral neuropathies.
A patent application is prepared and the “claims” to the patent are written to cover the exact piece of DNA for gene X as well as any and all variations that the scientist can come up with. The written document must conform to several statutory requirements. It must be sufficiently detailed so that a third person who knows something about the subject matter is clear that the scientist actually: a) described how to clone the particular gene, b) knows what its sequence is; c) knows how to create/clone any variants or homologs and at least figure out their sequences.

Each and every claim must describe something that obeys all terms of the patent triad: it must be “novel,” “non-obvious,” and “useful.” In effect, the patent lawyer and the U.S. Patent Office enter into a negotiation to craft claims such that their meaning defines something that obeys the triad. Let’s very briefly examine each one.

How could this receptor DNA be novel? It’s found in my own body!
The hypothetical states that the DNA was not located in any database. If the DNA was already described, the patent game would probably be over. However, more importantly for us is that the claims describe something not found in anyone’s body. A key concept that flows from the case law and from the patentability requirements for DNA is that the DNA must be “purified.” The claimed DNA is isolated away from all contaminating cells and other natural materials in a way it never would be in the human body. Thus, it is novel because it literally has not been described before in this form.

How could it be non-obvious? EVERYONE can do molecular biology these days!
The courts have struggled with this problem and it still is an important point. Remember, this hypothetical patent is for a chemical composition. The U.S. Patent Office and the courts have consistently taken the position that just because the method of producing the composition is known does not mean a compound is rendered unpatentable. This means that if someone is trying to patent a DNA sequence, as a sequence, the fact that DNA cloning and sequencing methods are trivial (such as by the use of gene sequencing machines) is not legally relevant to a determination whether the sequence itself is patentable. Certainly, overcoming difficulties in isolating and cloning the gene would strengthen the case for “non-obviousness” of the sequence and, possibly, would even allow claims to a novel method of cloning.

How could this DNA be useful if you have never used it for anything?
In order to get a patent on a purified piece of DNA, the scientist has to show that it has a “specific, substantial, and credible” utility. (See www.uspto.gov/web/offices/pac/utility/utilityguide.pdf). There are no hard and fast rules, and this “utility” requirement is taken up on a case-by-case basis. As long as our scientist is not going to try and patent a method of treating someone with the gene or with a protein encoded by the gene, he or she can probably get away with showing that the gene encodes a protein that has certain well known or experimentally-derived biological properties or perhaps that the gene can be used as a probe to clone other receptors.

With variations to a greater or lesser degree, this is the procedure and legal reasoning allowing one to get U.S. patents on DNA compositions, diagnostic gene testing kits, monoclonal antibodies, even transgenic animals. Once the Supreme Court allowed that genetically modified bacteria were proper subject matter for patents, transgenic animals became another “species” under this Chakrabarty “genus.”
Perhaps a decade hence, most of the important therapeutic genes will either be already patented or in public databases. Industry will turn increasingly to patenting therapeutic and diagnostic methods of using these already known (or patented) genes in order to gain exclusionary power and thus economic advantage. As concerned citizens, we should be asking the policy makers to what extent the economic cost of licenses and cross-licenses between the “gene holders” and the “gene users” will affect the health care system and the consumer.

The chart accompanying this article is not available online. Please email the editor for a copy.

Contact CRG for a footnoted version of this article.

Warren Kaplan has practiced intellectual property law for over 10 years, including a corporate position as Assistant General Counsel, Intellectual Property, at Biogen, Inc., Cambridge, Massachusetts and private practice positions at Choate, Hall & Stewart and Wolf, Greenfield & Sacks, P.C., both in Boston. Dr. Kaplan received his Ph.D. from Boston University and did research at Harvard University on the ecology of wetlands, biogeochemistry of greenhouse gases and global climate change.

 
 
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