September 2011
CIPA Journal
Authored by Anthony C. Tridico, Ph.D.
The patentability of isolated DNA molecules has been a tenet of U.S. patent law for over 30 years. The expansion of the biotechnology industry, sparked by scientific advances, was importantly supported by the Supreme Court's decision in Diamond v. Chakrabarty that a genetically engineered bacterium was patentable subject matter under § 101.1 And the U.S. Patent and Trademark Office (USPTO) has granted patents claiming isolated DNAs for almost 30 years − by some estimates issuing approximately 40,000 DNA-related patents by 2005.2 Against this backdrop, it is surprising that the U.S. courts have never addressed whether DNA-based claims are in fact eligible for patentability under 35 U.S.C. § 101. Now they have.
In Association for Molecular Pathology v. U.S. Patent and Trademark Office ("Myriad"), a three member panel of the U.S. Court of Appeals for the Federal Circuit affirmed the patentability of isolated DNA molecules in a highly anticipated decision.3 This paper reviews the background of the Myriad case and discusses the three separate opinions of the split Federal Circuit panel. While each of the judges relied largely on the same two precedential cases, Chakrabarty and Funk Bros.4 , their application of these cases to cDNAs, short DNAs such as primers and probes, and longer DNAs such as whole genes vary widely, as do their outcomes. Whether this question should be answered by the courts or the legislature is also addressed in each opinion, again with wildly differing results.
We also provide an update of the continued litigation of this case. Because of the importance of the issues at stake in Myriad, no one expected the Federal Circuit decision to be the final word, and indeed both parties have requested that the case be re-heard. Whether isolated DNA sequences will remain patentable when this case is finally resolved remains an open question.
The Myriad saga began in 2009, when twenty plaintiffs filed a lawsuit against the USPTO, Myriad Genetics, and the University of Utah challenging the validity of several patents related to two genes, BRCA1 and BRCA2. Certain mutations in the BRCA genes are diagnostic of an increased risk of breast and ovarian cancer, making these particular genes of special interest to patients, scientists and the medical community. The University of Utah owns or co-owns the seven challenged patents, which are exclusively licensed to Myriad. In the late 1990s, Myriad took aggressive and effective steps to enforce these patent rights: it is now the only source for clinical BRCA testing in the U.S. The Myriad plaintiffs − several medical associations, three medical researchers, breast cancer counselors, and women diagnosed with or seeking diagnosis − all claim to be adversely effected by Myriad's monopoly over BRCA testing.
The Myriad case was initially decided by the United States District Court for the Southern District of New York ("the Trial Court"). In a first decision, the Trial Court held that the court had jurisdiction over the plaintiffs − known as "standing" − to seek a declaratory judgment that Myriad's patents were invalid.5 Having determined that it could hear the lawsuit, the Trial Court, in a highly controversial decision, held that all of the challenged claims were not eligible for patenting, invalidating the patents.6 Myriad appealed both of the Trial Court's findings, arguing the plaintiffs lacked standing and the claims were eligible for patenting.
While the question of the court's jurisdiction is peripheral to the core patentability issues at stake in Myriad, it is highly relevant to the ongoing litigation (as discussed at the end of this article). The question of standing, a threshold issue for the case to be heard, is essentially whether any of the plaintiffs have "a substantial controversy of sufficient reality and immediacy" that can be redressed by a favorable decision.7
All three members of the Federal Circuit panel agreed that only one plaintiff had standing. Dr. Harry Ostrer, a research scientist at New York University, had received a demand from Myriad in 1998 for a royalty under its patents. Instead of continuing to perform BRCA testing himself, Ostrer began sending all patient samples directly to Myriad for diagnostic testing. Ostrer now has the expertise and resources to resume clinical BRCA testing, and "states unequivocally that he will immediately begin such testing" if Myriad's patents are invalidated.8 The other two scientists who previously conducted BRCA testing only stated that they would "consider" resuming testing; because their injuries were not sufficiently "actual or imminent," the Court found they lacked standing.9 Thus, the Court's ability to hear this case rests entirely on one plaintiff's allegation that he is able and intends to resume BRCA testing.
"Isolated" is the magic claim language used by most patent attorneys to differentiate the claimed invention from its counterpart, the naturally occurring gene sequence. Whether this word is sufficient to remove a DNA molecule from the unpatentable realm of nature and into the patentable world of man made inventions is the central issue in Myriad.
In the U.S., inventors can obtain a patent for "any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof . . . ."10 There are three judicially created exceptions: "laws of nature," "physical phenomena," and "abstract ideas" are not eligible for patenting. However, the Supreme Court's longstanding case law does not articulate clear tests for patent eligible subject matter. In some instances, materials purified from their natural setting have been found patentable, including adrenaline11 and vitamin B-12.12 In contrast, purified elements such as uranium and vanadium have been found patent ineligible.13
Two of the three judges on the Federal Circuit's panel, Judges Lourie and Moore, found all "isolated DNAs" are patentable subject matter. Judge Bryson dissented, finding cDNA sequences, which are not found in nature, are patent eligible, but finding any DNA with a chromosomal counterpart is not.
Writing for the majority, Judge Lourie relied heavily on the Supreme Court's decisions in Chakrabarty and Funk Bros. A genetically engineered bacterium was found patentable in Chakrabarty because the claimed bacteria had "markedly different characteristics from any [bacterium] found in nature".14 In contrast, a mixture of six bacterial strains with a newly recognized behavior was found ineligible for patentability in Funk Bros., where that behavior was "not a patentable advance because no species acquired a different property or use."15
Combining these precedents, Lourie writes: "[t]he distinction, therefore, between a product of nature and a human-made invention for purposes of §101 turns on a change in the claimed composition's identity compared with what exists in nature."16 The question is whether a composition - even if altered from its natural state - has "similar characteristics" as its natural counterpart, or whether as a result of human intervention the composition has "markedly different" or "distinctive" characteristics."17 It is not clear that this new test will be any easier to apply than its predecessors.
To analyze the claims being challenged, Lourie first describes the chemical structure of DNA, DNA isolation methods, and human genetics in great detail before comparing the claimed molecules to native DNA (i.e., as found in a chromosome). The sequence of a cDNA molecule is not found on any chromosome bearing the relevant gene, and thus all three judges agree that cDNAs are patent eligible. As Judge Moore states in her concurrence, "the claimed cDNA sequences do not exist in nature."18 Instead, they have a completely different nucleotide sequence than cellular RNA. "The claimed isolated cDNA sequences are the creation of man… [and] not one of the ‘manifestations of . . . nature, free to all men and reserved exclusively to none'" that falls outside of the patent system."19
Turning to isolated DNA molecules whose sequences are found on chromosomes, Lourie notes that such molecules can be synthesized (either recombinantly or chemically). Thus, "isolated DNAs" are not necessarily purified in the strictest sense. He also repeatedly emphasizes that such DNAs are different from chromosomal sequences because they have different chemical structures: the isolated molecules (even for very large genes) are significantly smaller than chromosomes, and they have different chemical bonds.20 For example, BRCA1 itself is about 80,000 nucleotides, but the native BRCA1 gene is found on chromosome 17, which has about 80 million nucleotides. To Lourie, this chemical difference is sufficient to render the isolated genes patent eligible: "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."21
In her concurring opinion, Moore also frames the patentability analysis using Chakrabarty and Funk Bros., which provide a "longstanding flexible approach" to determine whether an invention has markedly different characteristics with the potential for significant utility.22 However, she says that she writes separately "to emphasize certain chemical considerations," and her analysis is significantly different from Lourie's. In his opinion, Lourie did not address whether the claimed isolated DNA molecules have new functions. Moore, however, requires a "significant new utility as compared to nature" to find a composition patent eligible.23
Moore's description of the isolated DNA molecules reflects this focus. Compared to genomic sequences, the claimed DNAs have structural differences at their two ends (with a 5' hydroxyl group and a 3' phosphate group, instead of another nucleotide at each end), are substantially smaller than the same sequence found within a chromosome, and are created by man by either synthesis or by "chemically altering the larger polymer to cleave off adjacent portions."24 For the utility of isolated DNA molecules, Moore finds that by removing other "potentially confounding" sequences found in the chromosome, the isolated DNAs have additional utility, "particularly for the smaller isolated fragments" which are useful as probes and primers. Moore does not describe corresponding utilities of full length genomic sequences of isolated genes, such as for the creation of cell lines or transgenic animals useful for screening and identifying new drugs, for example.
Moore rejects Lourie's analysis of isolated DNA molecules with the same sequence as genomic DNA: "Although the different chemical structure does suggest that claimed DNA is not a product of nature, I do not think this difference alone necessarily makes isolated DNA so 'markedly different'."25 Instead, Moore asks whether these differences give the isolated DNA molecules a new utility. For shorter isolated DNAs, Moore finds that they satisfy this test because they are useful as primers and probes, for example, which chromosomal DNA is not, leading to a "different and beneficial utility."26
Moore struggles with patentability of longer isolated DNA molecules with genomic sequence, in part because she notes they are unsuitable for the two specific examples of utilities she described for short DNAs. She states that these longer DNAs "do not clearly lead to significant new utility as compared to nature."27 In the absence of a significant new utility, their patentability "depends on how much weight is allocated to the different structure as compared to the similarity of the function in nature."28
Ultimately, Moore finds that "settled expectations tip the scale in favor of patentability."29 These expectations include the property rights of the owners of thousands of issued patents with isolated DNA claims as well as the biotechnology industry. Concluding that it is the role of the legislature, not the courts, to decide whether isolated DNA molecules should be excluded from patent eligibility, she does not unsettle thirty years of expectations.30
Judge Bryson dissents from the majority, dismissing the significance of chemical differences between an isolated DNA molecule and its native chromosomal sequence.31 Bryson characterizes the structural differences as "irrelevant to the claim limitations" as well as their utility as isolated DNA, stating "there is no magic to a chemical bond. . ."32 Instead, he characterizes the isolated DNAs as simply "purified" molecules which do not acquire patentability by virtue of being extracted from their natural setting. Like his colleagues, Bryson applies the Chakrabarty test, but reaches the opposite conclusion: what is claimed in Myriad's patents "is the genetic coding material, and that material is the same, structurally and functionally, in both the native gene and the isolated form of the gene."33 In the absence of any differences, he finds isolated DNAs are not patentable subject matter.
The patent eligibility of two sets of method claims was also addressed by the Federal Circuit (with agreement by all three panel members). The first set of claims provide methods of detecting BRCA mutations by either "analyzing" or "comparing" sequences. The Court did not find these claims patent eligible. Such method claims have been the subject of several other recent cases, including Prometheus Laboratories Inc. v. Mayo Collaborative Services.34 The claims at issue in Prometheus, affirmed as patent eligible by the Federal Circuit, included the explicit recitation of "transformative" steps such as administering a drug to a body and determining its metabolism. In contrast, the Myriad comparing/analyzing claims only recited steps which can be accomplished by mere inspection of sequences, and the Court found they were directed to abstract mental processes, which are not patent eligible.
Only one of Myriad's method claims survived as directed to eligible subject matter. This "screening" claim recites several steps, including steps of (1) growing host cells under certain conditions, (2) determining their growth rate, and (3) comparing those rates.35 Because the first two steps are transformative, involving "physical manipulation of the cells," and those steps are "central to the purpose of the claimed process," the Court found they were not so abstract that they claimed only a scientific principle, and held the claim patent eligible.36 Consistent with other recent cases addressing biopharmaceutical method claims, this holding reiterates that when drafting U.S. claims, including explicit steps which require physical manipulations is essential for patentability.
The drama associated with the Myriad litigation has continued even after the Federal Circuit's decision in late July. Because this case has ramifications throughout the biotechnology industry, a petition for rehearing by the entire Federal Circuit or an appeal to the Supreme Court has been expected. Instead, both parties recently filed petitions to have the same Federal Circuit panel rehear the case.
The plaintiffs argue that the majority panel made several errors in its analysis by focusing on the structure of the isolated DNAs instead of their function. The plaintiffs maintain that the chemical structure of the isolated DNA is irrelevant for determining whether the DNA is patent eligible. "The claims have no express limitations to gene fragments that have had their covalent bonds broken by man, and such an inherent limitation is not supported by the specification, the file history, or any argument Myriad made at any time in this matter."
Myriad's rehearing brief contends that the case is now moot, because the sole plaintiff who was found by the Court to have standing has moved to a new research institution and now lacks standing. Two days before the Federal Circuit's July 29 decision, Myriad alerted the Court that Ostrer would leave New York University at the end of August and begin working at the Albert Einstein College of Medicine. In its responsive letter to the court, the plaintiffs countered that "Dr. Ostrer continues to wish to engage in [BRCA] sequencing…" Myriad argues that this "wish" or "desire" is a "someday intention" which cannot satisfy the Court's requirement for an immediate injury - as it did not for the other two researchers (who the plaintiffs argued in their own rehearing petition should also have standing).
With the Myriad decision, the U.S. Court of Appeals for the Federal Circuit has affirmed the patentability of isolated DNA molecules, including cDNA sequences, short primer and probe sequences, and longer DNAs such as whole genes. As this high profile and contentious litigation continues, however, whether an isolated DNA will ultimately remain patentable subject matter is unknown.
You can find more information on the Myriad decision on Finnegan's website at www.finnegan.com. You can also find more information on Federal Circuit Court Decisions at http://www.finnegan.com/publications/federalcircuit/.
Endnotes
1. 447 U.S. 303 (1980).
2. Rogers, "Can you patent genes? Yes and No," 93 J. U.S. Pat. & Trademark Off. Soc'y 19 (2010).
3. Assoc. for Molecular Pathology v. U.S. Patent & Trademark Office, 2010-1406 (Fed. Cir. 2011) (Bryson, J., dissenting).
4. Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948).
5. Assoc. for Molecular Pathology v. U.S. Patent & Trademark Office, 669 F. Supp. 2d 365 (S.D.N.Y. 2009).
6. Assoc. for Molecular Pathology v. U.S. Patent & Trademark Office, 702 F. Supp. 2d 181 (S.D.N.Y. 2009).
7. MedImmune v. Genentech Inc., 549 U.S. 118, 127 (2007).
8. Slip op. at 30.
9. Id.
10. 35 U.S.C. §101.
11. Parke-Davis & Co. v. H.K. Mulford Co., 189 F. 95 (S.D.N.Y. 1911).
12. Merck & Co. v. Olin Mathiesono Chem. Corp., 253 F. 2d 156 (4th Cir. 1958).
13. In re Marden, 47 F. 2d 957 (CCPA 1931); In re Marden, 47 F. 2d 958 (CCPA 1931).
14. Chakrabarty, 447 U.S. at 310.
15. Slip op. at 41, citing Funk Bros., 333 U.S. at 129-30.
16. Slip op. at 41.
17. Id.
18. Id. at 13.
19. Moore concurrence at 14.
20. Slip op. at 42.
21. Id.; emphasis added.
22. Moore concurrence at 7.
23. Id. at 18
24. Id. at 11.
25. Id. at 14; emphasis added
26. Id. at 16. Moore also urges that the dissent's analysis "would seem to support my conclusion that small isolated DNA molecules are directed to patentable subject matter." Id. at 17-18.
27. Id. at 18. The patentability of longer genomic sequences likely would have been a simpler analysis for Moore if she appreciated their various utilities, such as for gene therapy and the construction of cell lines or transgenic animals for drug screening.
28. Id. at 18.
29. Id. at 19.
30. Id. at 20-31.
31. Bryson dissent at 6.
32. Bryson dissent at 7, 13.
33. Id. at 13.
34. Prometheus Labs., Inc. v. Mayo Collaborative Servs., 628 F. 3d 1347 (Fed. Cir. 2010).
35. Slip op. at 53.
36. Slip op. at 54.
Originally printed in CIPA Journal. This article is for informational purposes, is not intended to constitute legal advice, and may be considered advertising under applicable state laws. This article is only the opinion of the authors and is not attributable to Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, or the firm's clients.
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