Contributed by: Justin Ellis
The United States Court of Appeals for the Federal Circuit recently issued a disturbing opinion regarding the patentability of isolated gene sequences in Ass'n for Molecular Pathology v. PTO, No. 2010-1406 (Fed. Cir. Jul. 29, 2011). While the Court went to great pains to explain the reasoning behind its decision affirming and reversing several different, prior rulings from the Southern District of New York, I am of the opinion that the Court completely missed the ball in reversing the prior court's holding that the defendant's patent claims over isolated DNA were invalid.
History Plaintiffs brought claim against Defendants Myriad Genetics, Inc. and the United States Patent and Trademark Office after Myriad began sending cease and desist letters to some of the Plaintiffs alleging that Plaintiffs were violating several of its patents in the genetics field. The Southern District of New York ruled for the Plaintiffs and Defendants appealed four of the District Court's rulings: (1) that the District Court had jurisdiction over the case; (2) that Myriad's patents directed to isolated DNA were invalid; (3) that Myriad's patents directed to comparing and analyzing gene sequences were invalid; and (4) that Myriad's patents directed to screening cancer treatment via cellular growth rates were invalid. The Court of Appeals affirmed rulings 1 and 3, and reversed rulings 2 and 4. This article will address only the reversal of ruling 2, regarding the validity of patents over isolated DNA sequences.
The Subject Matter The decision itself contains a wonderful primer regarding the structure and operation of DNA molecules that will have you flashing back to college biology class as you re-educated yourself about nucleotides, covalent bonds and other scientific concepts you probably forgot long ago. I recommend at least a quick perusal of the information in order to better understand the science behind this litigation, but I also try to explain it in a nutshell below.
Myriad's patents cover two “isolated” human genes, known as BRCA1 and BRCA2. The BRCA genes, once isolated, can be used as a standard of comparison against an individual's BRCA genes in order to identify genetic mutations that indicate a higher predisposition to cancer. Note that the patents at issue are over the genes themselves, not over the process to isolate the genes (which the Court says is common practice anyway).
To give a better idea of what is going on, consider a DNA molecule like a zipper. The two sides of the zipper are simply long strands of sugars and phosphate groups. Each of the “teeth” of the zipper can be one of four bases: Adenine (“A”) Cytosine (“C”) Guanine (“G”) or Thymine (“T”); These four bases (the “teeth”) will appear over and over again on one side of the zipper, and the sequence of bases on that side will bely the sequence of basis on the opposite side of the zipper, since each tooth only has one corresponding tooth that it can connect with to close the zipper (A always bonds with T, C always bonds with G). The sequence of As, Cs, Gs and Ts in a specific spot defines specific characteristics for an individual. For instance, if a person's body was making hair and that person's hair was brown, that color will be encoded in the person's DNA with a certain sequence bases appearing in a specific spot. The DNA will “unzip” so the sequence can be copied by messenger cells (“mRNA”) and those cells will take the copy off to wherever it needs to go and then perform (or help other cells perform) whatever it is the body needs to do to make brown hair. That specific spot of a specific sequence is a “gene,” because it defines a characteristic of the individual. An “isolated gene” then, is simply that sequence of A, C, G and T bases, all by itself and connected to one strand of sugars and phosphate groups that contains no other basis. Consider the following chart, which is simply my recreation of an example used by Judge Moore, in his partially-concurring opinion, to support the Court's belief that an isolated gene should be patentable (see Molecular Pathology, No. 2010-1406, Moore's Concurrence at 9-12):
What you see in the left part of the diagram is one-half of a DNA strand (one-half of the “zipper”), the sugar strand (in black) with a specific sequence of color-coded bases (from top to bottom, A-T-C-G-T). Note that the sugar strand ends, as it always does in DNA, with a phosphate group carrying a negatively-charged oxygen molecule on one end (the “5'” or “5 prime” end), and on the other end with a sugar molecule bonded with an oxygen and hydrogen molecule (the “3'” or “3 prime” end). These ends are always present in DNA, and the ends will always be opposite one another (i.e., if I had drawn the other half of this DNS molecule the sugar strand on the right side would have the 3' end at the top and the 5' end at the bottom).
The right part of the diagram shows only the second and third bases from the top (T-C) as they would look once isolated from the sugar strand. Note that the bases, the sugar strand and the sequence appear exactly as they do in nature, except that the bases are much closer to the DNA strand's 5' and 3' ends, since there are far fewer bases. The part of this decision being analyzed here involves whether one should be allowed to patent that isolated T-C section in the chart, so that no one else could use it.
Decision The question before the Court was whether the isolated DNA molecules themselves were patentable, or whether they fell under the “products of nature” exception, as the District Court ruled. The Court first talked about the exception, which was created by court decisions and does not appear in the actual statutes regarding patents, and noted that there are three exceptions to the generally broad group of things that are patentable: (1) laws of nature (also phenomena of nature); (2) abstract ideas (also mental processes); and (3) physical phenomena (also products of nature). The Court characterizes the distinction between a product of nature and human-made invention as “a change in the claim composition's identity compared with what exists in nature. Specifically... [there is] a line between compositions that, even if combined or altered in a manner not found in nature, have similar characteristics as in nature, and compositions that human intervention has given 'markedly different' or 'distinctive,' characteristics.” Molecular Pathology, No. 2010-1406, at 41. (Quoting Diamond v. Chakrabarty, 447 U.S. 303, 310 (1980).
The Opinion for the court went on to explain that the BRCA genes were man-made because “Myriad's claimed isolated DNAs exist in a distinctive chemical form – as distinctive chemical molecules – from DNAs in the human body...Native DNA exists in the body as one of forty-six large, contiguous DNA molecules...In each chromosome, the DNA molecule is packaged around proteins into a structure...which in turn is packaged into the chromosomal structure. Isolated DNA, in contrast, is a free-standing portion of a native DNA molecule, frequently a single gene. Isolated DNA has been cleaved (i.e., had covalent bonds in its backbone chemically severed) or synthesized to consist of just a fraction of a naturally occurring DNA molecule.” Molecular Pathology, No. 2010-1406, at 41-42. The opinion goes on to say, “The claimed isolated DNA molecules are distinct from their natural existence as portions of larger entities.” Id. at 44-45. in his concurrence, Judge Moore also pointed out that, in addition to the differences cited in the Court's Opinion, his example, reproduced in the graphics above, showed that isolated DNA molecules are different than native-DNA because base pairs that are normally plugged into the middle of the DNA strand might be plugged in at either end of the strand once they are isolated. See Molecular Pathology, No. 2010-1406, Moore's Concurrence at 9-12.
Analysis The problem with the Court's Opinion is that it confuses the separation of the gene from its natural environment with some kind of molecular transformation, and that molecular transformation (even if it exists) with human engineering. I do not buy the argument that a gene separated from other genes has undergone molecular transformation, because the gene has not really changed at all; this is evidenced by the fact that its whole purpose is to be compared to naturally occurring genes to look for mutations. If the isolated gene was somehow chemically altered, this process would not be possible. Saying that an isolated gene is “distinctly” or “markedly” different because it has been “cleaved” from its normal package of DNA, which natively sits inside a bunch of proteins that sits inside another, chromosome package is like saying that I can patent an “isolated” frog leg because, in nature, that frog leg is normally found attached to a frog, surrounded by mud that makes up a swamp, but now it is no longer attached to the frog, and it is no longer in the swamp, so I must have created something entirely different. I might also say that I can make frog leg soup with the isolated leg, and I cannot make frog leg soup with the entire frog, nor with the mud or the swamp, so my frog leg must be chemically altered from the naturally occurring frog.
Even if you buy the argument that the isolated gene is molecularly transformed, where is the human engineering? Any of the transformations are a result of naturally occurring phenomena, events that must occur as a natural result of a gene being removed from a larger strand of DNA. Again, I wholeheartedly agree that the process of separating the gene from the DNA would be patentable, as would the process of using the isolated gene to screen for cancer, assuming those processes were new and met other requirements of patentability, but simply cleaving a small piece of natural product from a larger piece of natural product does not make the smaller piece manmade.
Judge Bryson, in his concurrence, does a good job of arguing these points (Judge Bryson did not concur with the portion of the opinion concluding that isolated genes are patent-eligible subject matter). Bryson also points out that Myriad, the owner of the patents, was not the first to map the BRCA genes (i.e., it was not the one to find the location of the genes on the larger DNA molecules or in the even-larger chromosomes), and did not come up with the method it used to sequence the nucleotides (the method used to find out the order of the bases or “teeth” making up the genes), but was able to, as it was free to do, patent a number of different ways to apply its knowledge of the gene sequence as reward for the work it put in discovering the sequence. See Molecular Pathology, No. 2010-1406, Bryson's Concurrence at 3-4. Judge Bryson also points out that isolated lithium, like isolated DNA, requires bonds to be broken that hold the lithium to earth and more lithium and that, also like isolated DNA, isolated lithium has uses and applications that do not exist for lithium that has not been isolated. Judge Bryson then states that the Court, in dismissing the comparison between isolated DNA and isolated lithium by saying, “[isolated lithium] is the same element whether it is in the earth or isolated,” seems to have adopted the completely arbitrary rule that “Isolated atoms are not patent eligible, but isolated molecules are.” Id. at 8-9.
Conclusion The Court's own opinion sums it up nicely when it says, “Isolated DNA...consist[s] of just a fraction of a naturally occurring DNA molecule.” Molecular Pathology, No. 2010-1406 at 42. A “fraction” of a “naturally occurring” product or phenomena of nature does not, and never should, be considered eligible subject matter. Patents were created to protect new inventions and discoveries made by man, not pieces of nature that were simply “cleaved” away from the larger whole.
I, for one, would like to see this decision go to an en banc hearing, and possibly to the Supreme Court, though I have not seen anything to indicate one way or another whether this could be likely, or even a possibility (the fact that there are three separate decisions from the three judges might support a hearing en banc). Allowing entities to patent isolated genes could have far-reaching and potentially disastrous consequences for applications and industries we have just begun to fathom. For instance, if all isolated genes were patented by various entities (a real possibility now), scientists would have a much harder time experimenting to find causes and cures of genetic diseases. Doctors trying to introduce new genetic material designed to cure birth defects, physical wounds, or physical and mental diseases may be barred by a company's ownership of the genetic material involved, whether or not that company is doing anything with the genetic material or not, whether or not that company even discovered the genetic material in the first place. Again, the bottom line is that genes are naturally occurring, and the simple fact that they can be isolated but do not occur isolated in nature (as far as we know) does not suddenly turn them into man-made inventions.
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