Friday, July 29, 2011

Federal Circuit Upholds Patentability of Isolated Gene Sequences, But Not Methods for "Comparing" or Analyzing" Them

Today the Federal Circuit decided the Myriad gene patenting case, Association for Molecular Pathology v. USPTO.  The case involved the patentability of genes directed to detection of breast cancer (BRCA genes) and methods for using them.  The case attracted a great deal of publicity (and amicus briefs) because of the implications of allowing parties to patent such genes and methods.  Myriad's licensing activities didn't help its case -- according to the plaintiffs' complaint, Myriad's fees were so high for conducting diagnoses and licensing that many women could not afford the testing, and researchers were inhibited from doing further research in the area.

The 105-page decision included a majority opinion by Judge Lourie, a concurring opinion by Judge Moore, and a dissent in part by Judge Bryson.  Here's Judge Lourie's summary of his opinion:

On the threshold issue of jurisdiction, we affirm the district court’s decision to exercise declaratory judgment jurisdiction because we conclude that at least one plaintiff, Dr. Harry Ostrer, has standing to challenge the validity of Myriad’s patents. On the merits, we reverse the district court’s decision that Myriad’s composition claims to “isolated” DNA molecules cover patent-ineligible products of nature under § 101 since the molecules as claimed do not exist in nature. We also reverse the district court’s decision that Myriad’s method claim to screening potential cancer therapeutics via changes in cell growth rates is directed to a patent-ineligible scientific principle. We, however, affirm the court’s decision that Myriad’s method claims directed to “comparing” or “analyzing” DNA sequences are patent ineligible; such claims include no transformative steps and cover only patent-ineligible abstract, mental steps.

Judge Lourie's decision upheld the patentability of isolated DNA molecules.  His decision stated:

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. For example, the BRCA1 gene in its native state resides on chromosome 17, a DNA molecule of around eighty million nucleotides. Similarly, BRCA2 in its native state is located on chromosome 13, a DNA of approximately 114 million nucleotides. In contrast, isolated BRCA1 and BRCA2, with introns, each consists of just 80,000 or so nucleotides. And without introns, BRCA2 shrinks to just 10,200 or so nucleotides and BRCA1 to just around 5,500 nucleotides. Furthermore, claims 5 and 6 of the ’282 patent cover isolated DNAs having as few as fifteen nucleotides of a BRCA sequence. Accordingly, BRCA1 and BRCA2 in their isolated state are not the same molecules as DNA as it exists in the body; human intervention in cleaving or synthesizing a portion of a native chromosomal DNA imparts on that isolated DNA a distinctive chemical identity from that possessed by native DNA.
As the above description indicates, isolated DNA is not purified DNA. Purification makes pure what was the same material, but was previously impure. Although isolated DNA must be removed from its native cellular and chromosomal environment, it has also been manipulated chemically so as to produce a molecule that is markedly different from that which exists in the body. It has not been purified by being isolated. Accordingly, this is not a situation, as in Parke-Davis & Co. v. H.K. Mulford Co., in which purification of adrenaline resulted in the identical molecule being “for every practical purpose a new thing commercially and therapeutically.” 189 F. 95, 103 (C.C.N.Y. 1911). . . . In this case, the claimed isolated DNA molecules do not exist as in nature within a physical mixture to be purified. They have to be chemically cleaved from their chemical combination with other genetic materials. In other words, in nature, isolated DNAs are covalently bonded to such other materials. Thus, when cleaved, an isolated DNA molecule is not a purified form of a natural material, but a distinct chemical entity.
. . .
Because isolated DNAs, not just cDNAs, have a markedly different chemical structure compared to native DNAs, we reject the government’s proposed “magic microscope” test, as it misunderstands the difference between science and invention and fails to take into account the existence of molecules as separate chemical entities. The ability to visualize a DNA molecule through a microscope, or by any other means, when it is bonded to other genetic material, is worlds apart from possessing an isolated DNA molecule that is in hand and usable.

As to the patentability of the method claims for “comparing” or “analyzing” sequences, Judge Lourie's decision stated:

We conclude that Myriad’s claims to “comparing” or “analyzing” two gene sequences fall outside the scope of § 101 because they claim only abstract mental processes. . . . The claims recite, for example, a “method for screening a tumor sample,” by “comparing” a first BRCA1 sequence from a tumor sample and a second BRCA1 sequence from a non-tumor sample, wherein a difference in sequence indicates an alteration in the tumor sample. ’001 patent claim 1. This claim thus recites nothing more than the abstract mental steps necessary to compare two different nucleotide sequences: look at the first position in a first sequence; determine the nucleotide sequence at that first position; look at the first position in a second sequence; determine the nucleotide sequence at that first position; determine if the nucleotide at the first position in the first sequence and the first position in the second sequence are the same or different, wherein the latter indicates an alternation; and repeat for the next position.
. . .
Although the application of a formula or abstract idea in a process may describe patentable subject matter, id. at 3230, Myriad’s claims do not apply the step of comparing two nucleotide sequences in a process. Rather, the step of comparing two DNA sequences is the entire process claimed.
. . .
The claims thus fail to claim a patent-eligible process under § 101.

Finally, Judge Lourie upheld the patentability of the method claim directed to a method for screening potential cancer therapeutics:

Starting with the machine-or-transformation test, we conclude that the claim includes transformative steps, an “important clue” that it is drawn to a patent-eligible process. Bilski, 130 S. Ct. at 3227. Specifically, the claim recites a method that comprises the steps of (1) “growing” host cells transformed with an altered BRCA1 gene in the presence or absence of a potential cancer therapeutic, (2) “determining” the growth rate of the host cells with or without the potential therapeutic, and (3) “comparing” the growth rate of the host cells. The claim thus includes more than the abstract mental step of looking at two numbers and “comparing” two host cells’ growth rates. The claim includes the steps of “growing” transformed cells in the presence or absence of a potential cancer therapeutic, an inherently transformative step involving the manipulation of the cells and their growth medium. The claim also includes the step of “determining” the cells’ growth rates, a step that also necessarily involves physical manipulation of the cells.

Judge Moore's concurring opinion agreed with Judge Lourie on isolated cDNA sequences (which do not exist in nature), but had different thoughts about isolated DNA.  She first noted the complexity of dealing with the patenability of purified chemicals or elements.  Two prior cases had upheld the patentability of purified adrenaline and vitamin B-12; however, other cases had rejected patentability for purified uranium, vanadium, and ductile tungsten.  After discussing DNA technology, she stated:

The isolated DNA sequences at issue in this case have the same type of chemical changes, but on a much bigger scale. Instead of a string of five nucleotides, the chromosome is millions of base pairs; instead of a two-monomer molecule, the isolated molecules claimed in this case range from 15 nucleotides to thousands (or tens of thousands) of nucleotides. Nevertheless, like the simple sequences discussed above, just because the same series of letters appears in both the chromosome and an isolated DNA sequence does not mean they are the same molecule. While the isolated DNA molecules claimed in this case are undoubtedly inspired by the corresponding naturally occurring sequence present on the chromosome, man must create these isolated DNA molecules.
. . .
Isolation of a DNA sequence is more than separating out impurities: the isolated DNA is a distinct molecule with different physical characteristics than the naturally occurring polymer containing the corresponding sequence in nature.
. . .
DNA sequences that have the same pattern of DNA bases as a natural gene, in whole or in part, present a more difficult issue [than cDNA].  Unlike the isolated cDNA molecules, whose sequence is not present in nature, these kinds of isolated DNA claims include nucleotide sequences which are found in the human body, albeit as part of a much larger molecule, the chromosome.
. . .
Given the chemical differences highlighted by Judge Lourie’s opinion and discussed supra, the mere fact that the larger chromosomal polymer includes the same sequence of nucleotides as the smaller isolated DNA is not enough to make it per se a law of nature and remove it from the scope of patentable subject matter. The actual molecules claimed in this case are therefore not squarely analogous to unpatentable minerals, created by nature without the assistance of man. Instead, the claimed isolated DNA molecules, which are truncations (with different ends) of the naturally occurring DNA found as part of the chromosome in nature, are not naturally produced without the intervention of man.
. . .
The shorter isolated DNA sequences have a variety of applications and uses in isolation that are new and distinct as compared to the sequence as it occurs in nature. For example, these sequences can be used as primers in a diagnostic screening process to detect gene mutations. These smaller isolated DNA sequences—including isolated radiolabeled sequences mirroring those on the chromosome—can also be used as the basis for probes. Naturally occurring DNA cannot be used to accomplish these same goals. Unlike the isolated DNA, naturally occurring DNA simply does not have the requisite chemical and physical properties needed to perform these functions.

Finally, Judge Moore relied on the Patent Office's long-standing practice to allow patents on such genes, and said that Congress should address the issue instead of the courts.  "The patents in this case might well deserve to be excluded from the patent system, but that is a debate for Congress to resolve. I therefore decline to extend the “laws of nature” exception to include isolated DNA sequences."

Judge Bryson agreed with Judges Lourie and Moore as to the method claims and cDNA, but dissented as to isolated DNA.

In its simplest form, the question in this case is whether an individual can obtain patent rights to a human gene. From a common-sense point of view, most observers would answer, “Of course not. Patents are for inventions. A human gene is not an invention.” The essence of Myriad’s argument in this case is to say that it has not patented a human gene, but something quite different—an isolated human gene, which differs from a native gene because the process of extracting it results in changes in its molecular structure (although not in its genetic code). We are therefore required to decide whether the process of isolating genetic material from a human DNA molecule makes the isolated genetic material a patentable invention. The court concludes that it does; I conclude that it does not.
. . .
Yet some of Myriad’s challenged composition claims effectively preempt any attempt to sequence the BRCA genes, including whole-genome sequencing. In my view, those claims encompass unpatentable subject matter, and a contrary ruling is likely to have substantial adverse effects on research and treatment in this important field.
. . .
Myriad’s claims to the isolated BRCA genes seem to me to fall clearly on the “unpatentable” side of the line the Court drew in Chakrabarty. Myriad is claiming the genes themselves, which appear in nature on the chromosomes of living human beings. The only material change made to those genes from their natural state is the change that is necessarily incidental to the extraction of the genes from the environment in which they are found in nature. While the process of extraction is no doubt difficult, and may itself be patentable, the isolated genes are not materially different from the native genes. In this respect, the genes are analogous to the “new mineral discovered in the earth,” or the “new plant found in the wild” that the Supreme Court referred to in Chakrabarty. It may be very difficult to extract the newly found mineral or to find, extract, and propagate the newly discovered plant. But that does not make those naturally occurring items the products of invention.
. . .
The principles underlying that analysis [isolating lithium, which doesn't appear by itself in nature] apply to genetic material as well. In order to isolate the BRCA gene, it is necessary to break chemical bonds that hold the gene in its place in the body, but the genetic coding sequence that is the subject of each of the BRCA gene claims remains the same whether the gene is in the body or isolated. The majority, however, does not agree that the cases are analogous, and indeed appears to have adopted the following rule: Isolated atoms are not patent eligible, but isolated molecules are.
. . .
The structural differences between the claimed “isolated” genes and the corresponding portion of the native genes are irrelevant to the claim limitations, to the functioning of the genes, and to their utility in their isolated form. The use to which the genetic material can be put, i.e., determining its sequence in a clinical setting, is not a new use; it is only a consequence of possession. In order to sequence an isolated gene, each gene must function in the same manner in the laboratory as it does in the human body. Indeed, that identity of function in the isolated gene is the key to its value. Moreover, as Judge Moore’s concurring opinion explains, Myriad has failed to credibly identify new uses for the isolated BRCA genes as probes or primers. The naturally occurring genetic material thus has not been altered in a way that would matter under the standard set forth in Chakrabarty. For that reason, the isolation of the naturally occurring genetic material does not make the claims to the isolated BRCA genes patent-eligible.

There's lots more in this lengthy opinion.  Given the stakes of this case and the three separate opinions it generated, (1) it's more likely than usual that the Federal Circuit will rehear the case en banc (that Court very rarely hears cases en banc), and (2) Supreme Court review is also far more likely than usual (at least of the decision to allow patents on isolated genes).
Here's Patently-O's discussion.  Techdirt's discussion is here.

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