On July 29, 2011, the Federal Circuit issued its decision in Association for Molecular Pathology v. USPTO, also known as the ACLU/Myriad “gene patenting” case. In a mixed decision, the court held that “isolated DNA” claims are patent-eligible under 35 USC § 101, but that the “comparing” or “analyzing” method claims are not. With a 55 page opinion authored by Judge Lourie, a 31 page concurrence-in-part authored by Judge Moore, and a 19 page dissent-in-part authored by Judge Bryson, there is much to be analyzed before the full impact of this decision—and the contours of the holdings—will be understood.
Myriad owns or is the exclusive licensee of a series of patents claiming isolated DNA compositions and methods for testing for the presence of genetic mutations that are correlated with an increased risk of certain breast and ovarian cancers (the BRCA1 and BRCA2 genes). A coalition of plaintiffs, led by the ACLU, challenged the claims as encompassing patent-ineligible subject matter, e.g., products of nature.
On appeal, Myriad challenged two decisions by the district court: the denial of Myriad’s motion to dismiss for lack of standing and subject matter jurisdiction, and the grant of summary judgment in ACLU’s favor on invalidity under § 101.
The threshold issue address by the court was standing. The court first noted a three-part test for standing based on the Supreme Court’s 1992 decision in Lujan v. Defenders of Wildlife:
First, the plaintiff must have suffered an injury in fact—an invasion of a legally protected interest which is (a) concrete and particularized, and (b) actual or imminent, not conjectural or hypothetical
Second, there must be a causal connection between the injury and the conduct complained of—the injury has to be “fairly . . . trace[able] to the challenged action of the defendant . . . .”
Third, it must be “likely,” as opposed to merely “speculative,” that the injury will be “redressed by a favorable decision.”
The court also cited a two-part test for declaratory judgment jurisdiction in patent cases based on its 2005 decision in MedImmune, Inc. v. Centocor, Inc.:
a declaratory judgment plaintiff must allege both (1) an affirmative act by the patentee related to the enforcement of his patent rights . . . and (2) meaningful preparation to conduct potentially infringing activity.
The court found that Dr. Ostrer satisfied this test, as he had received (in 1988) a letter from Myriad demanding royalty payments for his BRCA1 diagnostic testing services, and because he had alleged “an intention to actually and immediately engage in allegedly infringing BRCA-related activities.”
The court’s decision on this issue was unanimous.
(As Kevin Noonan wrote on Patent Docs, the parties disagree as to whether Dr. Ostrer’s imminent employment change impacts his standing.)
The “Isolated DNA” Claims
Writing for the court, Judge Lourie read the 1980 Supreme Court decision in Diamond v. Chakrabarty and earlier Supreme Court decisions such as Funk Brothers (1948) as providing this framework for applying 35 USC § 101:
The distinction, therefore, between a product of nature and a human-made invention . . . turns on a change in the claimed composition’s identity compared with what exists in nature. Specifically, the Supreme Court has drawn 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.
Applying this test to the isolated DNAs in this case, we conclude that the challenged claims are drawn to patentable subject matter because the claims cover molecules that are markedly different—have a distinctive chemical identity and nature—from molecules that exist in nature.
Basically, Judge Lourie applied the “breaking covalent bonds” test that he had raised during oral argument.
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. . . . 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.
In reaching this decision, Judge Lourie went to great lengths to distinguish “isolated” DNA from a “purified” product:
[I]solated 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. . . . 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. . . . Thus, when cleaved, an isolated DNA molecule is not a purified form of a natural material, but a distinct chemical entity.
While the opinion does not go so far as to say that a “purified” substance would not satisfy § 101 (and if it did, that would have been dicta), the discourse certainly indicates that the court might not look favorably on claims drawn to purified products that occur in nature, such as proteins and antibodies.
(The USPTO has not drawn such a distinction between “isolated DNA” and, for example, “purified” proteins, and has treated both as being distinguished from products of nature as required by § 101.)
Judge Moore concurred in this part of the decision, but wrote separately to explain additional/alternate views for finding that the “isolated DNA” claims satisfy § 101.
Judge Bryson dissented from this part of the decision as applied to isolated genomic DNA sequences, but would have upheld the patent-eligibility of the cDNA claims.
The “Comparing”/”Analyzing” Method Claims
The court identified two method claims as representative of the “comparing”/”analyzing” claims:
1. A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Ta-bles 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1.
1. A method for screening a tumor sample from a human subject for a somatic alteration in a BRCA1 gene in said tumor which comprises  comparing a first sequence selected from the group consisting of a BRCA1 gene from said tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA from said tumor sample with a second sequence selected from the group consisting of BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from said nontumor sample and BRCA1 cDNA made from mRNA from said nontumor sample, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said tumor sample from the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said nontumor sample indicates a somatic alteration in the BRCA1 gene in said tumor sample.
The court found that these claims do not satisfy § 101 because “they claim only abstract mental processes.”
In reaching this decision, the court rejected Myriad’s arguments that the claims inherently embodied transformative steps that satisfied § 101, such as “(1) extracting DNA from a human sample” and “(2) sequencing the BRCA DNA molecule,” because such steps “necessarily precede the step of comparing nucleotide sequences.” The court noted that the claims did not recite such steps, or “specify any action prior to the step of ‘comparing’ or ‘analyzing’ two sequences.”
The court distinguished its recent decision in Prometheus Laboratories, Inc. v. Mayo Collaborative Services, where it upheld certain method claims as reciting a transformative “determining” step because “[s]ome form of manipulation, such as the high pressure liquid chromatography method specified in several of the asserted dependent claims . . . is necessary to extract the metabolites from a bodily sample and determine their concentration.”
Myriad’s claims . . . do not include the step of “determining” the sequence of BRCA genes by, e.g., isolating the genes from a blood sample and sequencing them, or any other necessarily transformative step. Rather, the comparison between the two sequences can be accomplished by mere inspection alone. Accordingly, Myriad’s claimed methods of comparing or analyzing nucleotide sequences fail to satisfy the machine-or-transformation test, and are instead directed to the abstract mental process of comparing two nucleotide sequences.
The court’s decision on this issue was unanimous.
(I think it is important that the court decided this issue on the “abstract mental process” ground rather than the “natural phenomenon” ground. In so doing, the court leaves the door open for claims directed to similar methods—genetic screening methods, companion diagnostic methods, etc.—as long as the claims look more like the Prometheus claims than the Myriad claims. It will be interesting to see if the Supreme Court follows the Federal Circuit’s lead when it decides Prometheus, or at least recognizes that the rationale here provides an alternative basis for restricting patent-eligibility on a case-by-case basis.)
The Drug Screening Claim
The court considered, and upheld, a claim directed to screening drug candidates:
20. A method for screening potential cancer therapeutics which comprises:
growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic,
growing said transformed eukaryotic host cell in the absence of said compound,
determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and
comparing the growth rate of said host cells,
wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.
The court found that this claim easily satisfied the machine-or-transformation test, and also found that it “is not so ‘manifestly abstract’ as to claim only a scientific principle. To the contrary, “it is tied to specific host cells transformed with specific genes and grown in the presence or absence of a specific type of therapeutic,” and “is tied to measuring a therapeutic effect on the cells solely by changes in the cells’ growth rate.” Thus, the claim satisfies § 101.
The court’s decision on this issue was unanimous.
A Mixed Reaction To This Mixed Decision
I have a mixed reaction to this decision. While the decision on the “isolated DNA” claims maintains the status quo, the way the court drew a line between “isolated DNA” and other “purified” products of nature would be a departure from current USPTO practice if implemented as an interpretation of § 101. Likewise, while I am not surprised by the court’s decision on the “comparing”/”analyzing” claims, I think that was a “sleeper” issue that was overshadowed by the unusual public attention given to the DNA claims.
It is likely that at least Plaintiffs-Appellees will request rehearing en banc at the Federal Circuit and/or petition for certiorari to the Supreme Court, so I doubt that this is the last word on the Myriad claims. Still, practitioners and patent holders in the biotech and personalized medicine fields probably will be reviewing and evaluating their patent claims in view of this Federal Circuit decision.
For additional analysis of this decision and other personalized medicine issues, please visit the Personalized Medicine Bulletin edited by Antoinette Konski and Jacqueline Wright-Bonilla, my colleagues at Foley & Lardner LLP. My colleague Hal Wegner also has authored a paper with a critical analysis of this decision.