Subject Matter Patent-Eligibility of Isolated DNA and Diagnostic Methods Addressed Head-on

On Friday, July 29, 2011, in one of the most controversial and publicized biotech patent cases in recent years, the Federal Circuit decided the “ACLU/Myriad” gene patenting case, formally known as Assn. Molec. Path. et al. v. USPTO et al. In a majority opinion by Judge Lourie, the court addressed the case on the merits, after finding that at least one plaintiff had standing to sue. The court held all “isolated DNA” claims at issue patent-eligible, but held as patent-ineligible diagnostic method claims that in effect recited only “comparing” or “analyzing” DNA sequences. While this ruling could ultimately be subject to en banc review before all judges at the Federal Circuit and/or find its way to the Supreme Court, this decision now and its impact will undoubtedly be of great interest to everyone working in the biotechnology and diagnostic medicine fields.

Background

After hearing oral arguments on April 4, 2011, Judges Lourie, Bryson, and Moore at the Federal Circuit issued opinions relating to the appeal of the March 29, 2010 summary judgment decision of the U.S. District Court for the Southern District of New York (Sweet, J.) that invalidated fifteen challenged claims in seven Myriad patents as patent-ineligible under 35 U.S.C. § 101. Notably, all three Federal Circuit judges wrote separate opinions, culminating in a grand total of 105 pages of text.

Standing Found for One Plaintiff

In the majority opinion, Judge Lourie first addressed the issue of standing. The finding of standing here is particularly interesting because the court could have dodged the ball and declined to address the merits. The court did not dodge, however, and affirmed the district court finding of declaratory judgment jurisdiction. The court found that at least one plaintiff, Dr. Harry Ostrer, had standing to challenge the validity of Myriad’s patents. Applying the Supreme Court’s test in MedImmune v Genentech(2007), the Federal Circuit determined that at least Dr. Ostrer alleged an intention to actually and immediately engage in allegedly infringing activity. Unlike other plaintiffs who merely alleged that they would “consider” engaging in relevant testing, Dr. Ostrer “not only has the resources and expertise to immediately undertake clinical BRCA testing, but also states unequivocally that he will immediately begin such testing.” Interestingly, Myriad and commentators have recently raised issues regarding Dr. Ostrer’s continued standing in this case, as Dr.Ostrer has changed jobs, which may be relevant to his ability to make or use allegedly infringing tests.

Isolated DNA Composition Claims Are Patent-Eligible

On the merits, the court held that Myriad’s composition claims directed to “isolated” DNA molecules refer to patent-eligible subject matter under 35 U.S.C. §101. In reversing the district court, the Federal Circuit refused to find “isolated DNA” patent-ineligible products of nature, because such molecules as claimed do not exist in nature.

Citing the Supreme Court’s decisions in Chakrabarty and Funk Brothersas “set[ting] out the framework for deciding the patent eligibility of isolated DNA molecules,” Judge Lourie noted that the distinction “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.” Specifically, one must consider whether “human intervention has given ‘markedly different,’ or ‘distinctive,’ characteristics.” Applying this test, the court concluded that isolated DNA claims relate to molecules that “are markedly different — have a distinctive chemical identity and nature — from molecules that exist in nature.” In this analysis, the court discounted Plaintiffs’ approach of only considering the “information content,” i.e., sequence information, contained in isolated and native DNA, or the fact that DNA molecules genetic function is to transmit information.

The court discussed how isolated DNAs exist in a distinctive chemical form, i.e., as distinctive chemical molecules, as compared to DNA in the body. Noting that “isolated DNA is not purified DNA,” the Court explained:

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.

The court further stated:

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. In fact, some forms of isolated DNA require no purification at all, because DNAs can be chemically synthesized directly as isolated molecules.

Interestingly, this passage relates to Judge Lourie’s proposed “breaking of covalent bond” test that he raised during oral argument.

In addition, the court also rejected the U.S. Department of Justice’s (DOJ) proposed “magic microscope” test. Under this test, the DOJ would find isolated DNA claims reciting cDNA and other non-native sequences patent-eligible, but isolated DNA claims reciting native genomic sequences patent-ineligible. The majority opinion stated that this proposed test “misunderstands the difference between science and invention and fails to take into account the existence of molecules as separate chemical entities.” As the court explained, 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… Visualization does not cleave and isolate the particular DNA; that is the act of human invention.”

“Growing” and “Determining” Method Claim Held Patent-Eligible

The court also reversed the district court’s decision regarding Myriad’s method claim directed to screening potential cancer therapeutics comprising at least the steps of “growing a transformed eukaryotic host cell” and “determining the rate of growth of said host cell.” See claim 20 of U.S. Pat. No. 5,747,282 and other diagnostic method claims in pending and decided cases relevant to personalized medicine.  Unlike other method claims at issue, the court found this method claim patent-eligible under §101. As relating to the “growing” and “determining” steps, the court found that the claim “includes transformative steps, an ‘important clue’ that it is drawn to a patent-eligible process,” citing the Supreme Court’s decision in Bilski v. Kappos (2010).

“Comparing” or “Analyzing” Diagnostic Method Claims Held Patent-Ineligible

In a move to be noticed by the personalized medicine community, the court affirmed the district court’s finding of patent ineligibility regarding certain method diagnostic claims.

Method claims found ineligible here recite, for example, (1) a method for detecting a mutation in a gene comprising the step of “analyzing a sequence” of a gene from a human sample, or (2) a “method for screening germline of a human subject for an alteration” in a specific gene comprising the step of “comparing germline sequence” of a particular gene from a tissue sample with wild-type sequences. According to the court, such claims are patent-ineligible because “they claim only abstract mental processes.”

The court rejected Myriad’s argument that the methods necessarily embodied transformative steps, similar to the claims recently upheld in Prometheus. Noting that while the Prometheus claims recited a “determining” step that embodied a transformation, the Myriad claims at issue here did not.

Judge Moore’s and Judge Bryson’s Additional Opinions

While agreeing with Judge Lourie’s opinion regarding standing and the holdings pertaining to method and isolated cDNA claims, both Judge Moore and Judge Bryson authored separate opinions regarding patent eligibility of isolated genomic DNA composition claims, with Judge Moore concurring on additional grounds and Judge Bryson dissenting.

Although Judge Moore agreed that all isolated DNA claims recited patent-eligible subject matter, she wrote separately to express her views that “Funk Brothers and Chakrabarty do not stake out the exact bounds of patentable subject matter. Instead, each applies a flexible test…” She also suggested that the fact that a claimed DNA is not a product of nature by itself does not make it so “markedly different” as to satisfy §101. Rather, one should consider whether chemical differences impart a new and significant utility, i.e., “markedly different” characteristics/properties.  Under this test, she found claims directed to cDNA or isolated genomic DNA short fragments to be patent-eligible, while claims encompassing the isolated full-length gene were “a much closer call.”  Ultimately, Judge Moore was persuaded by Congress’ and USPTO’s long-standing authorization of an expansive scope of patentable subject matter, as well as the fact that Congress has remained silent on this issue.

Like Judge Lourie, Judge Moore acknowledged but discounted the DOJ’s proposed “magic microscope” test. As stated in her concurring opinion, “[c]ertainly the magic microscope has curb appeal—its child-like simplicity an apparent virtue. The magic microscope, however, would not see the claimed DNA molecules at issue in this case.” Moreover, “[w]hile the magic microscope creates a bright line rule, it presents a poorly defined question: can we “see” the claimed molecule, or something fairly similar, in nature?” Judge Moore found this test to be contrary to the proper inquiry under Chakrabarty and Funk Brothers. Along these lines, she concluded that the DOJ incorrectly asked the court to “do away with Chakrabarty’s flexible inquiry as to whether the invention, as claimed, has ‘markedly different characteristics from any found in nature’ which result in ‘the potential for significant utility.’”

In his opinion concurring-in-part and dissenting-in-part, Judge Bryson opined that relevant composition claims directed to native genomic DNA, including those reciting gene fragments, were ineligible for patent protection. Judge Bryson would find claims directed to cDNA patent-eligible, however, in line with the DOJ’s position. Notably, however, unlike the other two judges, Judge Bryson did not mention nor analyze the DOJ’s “magic microscope” test. In fact, he did not say much at all about the DOJ position except to note that it argued that Myriad’s composition claims, other than cDNA claims, were not patent-eligible, and Judge Bryson believes that the Executive Branch “has modified its position from the one taken by the PTO in its 2001 guidelines and, informally, before that.”

Looking Ahead

This decision will be of great interest to the biotech community and to those generally following patent jurisprudence on the subject matter eligible for patent protection under §101. It is expected that at least the ACLU/Plaintiffs will consider a request for a rehearing en banc at the Federal Circuit and/or petition for certiorari at the Supreme Court, which is currently considering the Prometheus case.

Please look for future posting on the Personalized Medicine Bulletin and PharmaPatentsblogs for further analysis and updates.  Along these lines, please see an article by our Foley & Lardner colleague, Courtenay Brinckerhoff, entitled “Federal Circuit Issues Mixed Decision On Myriad Claims.”