High Court's Myriad Questions Suggest Isolated DNA Patent Eligibility in Doubt

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By Tony Dutra  


Supreme Court justices found few answers from the parties or the government in the attempt April 15 to distinguish, for purposes of patent eligibility under 35 U.S.C. §101, genetic materials from unpatentable “products of nature” (Association for Molecular Pathology v. Myriad Genetics Inc., U.S., No. 12-398, argued 4/15/13).

Solicitor General Donald B. Verrilli Jr. joined attorneys from the American Civil Liberties Union and Myriad Genetics Inc. in dodging questions during oral argument about molecular differences between isolated DNA and genomic DNA in the human body, and whether investment in biotechnology innovations would be different if only complementary DNA, and not isolated DNA, were patent eligible.

The government, without buy-in from the Patent and Trademark Office, has continually tried to cite differences between the two, and several justices appeared ready to accept that cDNA was human engineered and isolated DNA was not. Though many of the justices' queries went unanswered, making a prediction difficult, the court seemed to lean toward the government's view.

Justice Clarence Thomas was once again silent, but the other eight justices challenged each party, and four of the justices challenged Verrilli despite his limited time to present.

Perhaps of greatest concern to the patent community outside the biotechnology context, the court's Mayo v. Prometheus decision, despite its unanimous vote in the court, took some hits. When any of the counsel prefaced comments with the equivalent of “… as this court said in Mayo …,” the justices distinguished the case, if they considered the reference at all.

One practitioner told BNA after the session that the justices surprised him in coming a long way compared to their performance in recent Section 101 oral arguments.

“They were so well prepared for this one, both in terms of patent law and biotechnology,” according to Michael Samardzija, of Bracewell & Giuliani, Houston. “They really got the nuances of the issues here.”

Challenge Began in 2009

The case arose from a 2009 declaratory judgment challenge filed by the ACLU and the Public Patent Foundation on behalf of several associations and individual plaintiffs (91 PTD, 5/14/09).

The case involves seven patents (U.S. Patent Nos. 5,747,282; 5,837,492; 5,693,473; 5,709,999; 5,170,001, 5,753,441; and 6,033,857) on isolated DNA, complementary DNA, and methods related to the BRCA1 and BRCA2 genes. The specific gene sequences claimed in the patents correlate with a likelihood of breast and ovarian cancer. The patents are owned or part-owned by the University of Utah Research Foundation, and Myriad is the exclusive licensee.

The district court held that the 15 challenged claims were ineligible for patenting under Section 101 (60 PTD, 3/31/10), but the Federal Circuit overturned that decision in large part.

In its first decision in July 2011, the three members of a Federal Circuit panel agreed that only one of the method claims and all the claims to cDNA were patent eligible, but the court was divided as to claims to isolated DNA, referred to by some as genomic DNA or gDNA (150 PTD, 8/4/11).

Then in March 2012, a week after unanimously rejecting medical diagnostic method claim patent eligibility in Mayo Collaborative Services v. Prometheus Laboratories Inc., 132 S. Ct. 1289, 101 U.S.P.Q.2d 1961 (2012) (55 PTD, 3/22/12), the Supreme Court granted the ACLU's first petition for writ of certiorari in the instant case, vacated the Federal Circuit's opinion, and remanded the case for reconsideration (60 PTD, 3/29/12).

Federal Circuit Judges Stand Pat

On remand, however, the appeals court panel came to the same conclusions and, in August, each of the three judges--the court's opinion was written by Judge Alan D. Lourie--issued essentially the same opinions that they had penned the first time. Association for Molecular Pathology v. U.S. Patent and Trademark Office, 689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012) (159 PTD, 8/17/12).

The ACLU petitioned again for certiorari in September. The petitioners sought review of three questions: one related to isolated DNA, one on method claims, and a third on standing.

In November, the Supreme Court certified only the first question presented: “Are human genes patentable?”.

Briefs, including active amici participation, were filed beginning in January and ending in March. The U.S. government, without anyone from the PTO signing the brief, essentially agreed with the dissent in the Federal Circuit's decision, that isolated genomic DNA is not patent eligible but cDNA is.

The U.S. Solicitor General's Office was given the opportunity to argue before the justices.

Amazon Plant Analogy Takes Prominence

“What exactly did Myriad invent?,” Christopher A. Hansen, staff attorney with the ACLU's Speech, Privacy, and Technology Project, arguing on behalf of the declaratory judgment plaintiffs and petitioners, began. “Nothing,” he answered. “Myriad unlocked the secrets of two human genes. But the genes themselves … were made by nature, not by Myriad.”

The petitioners's primary argument throughout the case has been that all patent claims on DNA as a composition of matter fall under an exception to patent eligibility as “products of nature.” Though that term is not specifically listed as one of the three judicially-created exemptions to Section 101--“laws of nature, natural phenomena, and abstract ideas,” according to Diamond v. Chakrabarty, 447 U.S. 303, 206 U.S.P.Q. 193 (1980)--the court accepted throughout oral argument that a “product of nature doctrine” constrains the composition of matter category.

Since the initial briefing in the district court, briefs and arguments have featured a war of analogies. In front of the nine justices, Hansen tried an analogy to gold first. You can patent using gold to make earrings, he said, but that does not make you eligible for a patent on gold. But that analogy received little air time.

Justice Samuel A. Alito had the honor of introducing the analogy that most took hold: discovering that a molecule in a leaf of a plant found in the Amazon has medicinal purposes.

Patents on Use vs. Composition

Hansen tried to simplify the analogy, saying there would be no patent eligibility if one simply took the leaf and swallowed it. He allowed that the chemical would be patent eligible if it were extracted and made available in more concentrated form.

Alito would not accept the answer, failing to see the distinction between that extraction and isolating DNA. To Alito, the extraction and isolation gave the DNA here a different function from what it had in the human body, just as the extracted--and consequently concentrated--tree sap would have.

Hansen now distinguished the uses from the DNA molecule. The petitioners did not challenge several claims for use of genetic material as probes and primers. But Hansen said, the isolated DNA here is being claimed for the function of looking at it, and that distinguishes the eligible use from the ineligible composition of matter.

Justices Elena Kagan and Anthony M. Kennedy tried to get Hansen to distinguish other claims--both those at issue and those not challenged by the plaintiffs in this case--but his answers failed to satisfy them. Fortunately for Hansen, Justice Sonia M. Sotomayor, the most persistent questioner throughout the oral argument, came to his rescue.

“That's the whole point, isn't it? The isolation itself is not valuable; it's the use you put the isolation to,” she said. “That's the answer, isn't it?”

“That's exactly correct,” Hansen said. “Thank you. Yes, that is the answer.”

“And so, that is the answer, which is in isolation it has no value,” Sotomayor concluded. “It's just nature sitting there.”

Later, though, Gregory A. Castanias of Jones Day, Washington, D.C., arguing for Myriad, rejected the view that a composition of matter claim must be tied directly to a specific use. He reminded the justices of the court's ruling in Brenner v. Manson, 383 U.S. 519, 148 U.S.P.Q. 689 (1966), “that you do not need to call out the utility of an invention in a particular claim. What you do have to do is have utility for the invention itself described in the specification.”

He said that the Federal Circuit has repeatedly followed that guidance and the PTO clarified that point in 2001 in its Final Examiner Guidelines on Utility Requirement, 66 Fed. Reg. 1,092 (Jan. 5, 2001).

PTO vs. Solicitor General?

That argument brought up a difficult issue for Myriad, though: The government's current position rejects the PTO's guidelines with respect to isolated DNA patents.

Myriad based much of its brief and Castanias focused in his presentation on the settled expectations of the patent and biotechnology communities in relying on patent grants on claims to isolated DNA. In his opening statement, Castanias said, “It is now 33 years after Chakrabarty, 31 years after the first isolated gene molecule patents issued, and 12 years after the Patent and Trademark Office issued its carefully reasoned Utility Guidelines confirming that new isolated gene molecules are eligible for patents, and it's almost 16 years after Myriad's patents began to issue,” he began.

But in light of the government's current position, Justice Ruth Bader Ginsburg said, “the strength of the presumption would be diluted.”

Castanias still called for deference to the PTO rather than to the Solicitor General's Office.

Uses vs. Composition Claims

Kagan changed the topic back to the issue of use versus composition, though, and caught Castanias off guard. She asked whether the first person to discover a chromosome deserved a patent.

Castanias, almost reluctantly, said, “If it had use. If it had a new utility, then yes.”

Kagan said she expected the answer at least in part because “the PTO seems very patent happy,” but, she added, “then it's not a question about, you know, breaking these covalent bonds or whatever Judge Lourie thought it was about. Right? So, you know, if not DNA, if not the smaller unit in the chromosome, you know, we could just go up from there and talk about all kinds of parts of the human body, couldn't we? Couldn't we get to, you know, the first person who found a liver?”

Everything Is Found in Nature

Castanias struggled with the answer and that brought Justice Stephen G. Breyer into the conversation. Breyer, who wrote the court's opinion in Mayo, questioned the extent of Myriad's thinking: “I mean, all parts of the human body? Anything from inside the body that you snip out and isolate?”

When Castanias said no, because a liver would be the same inside and outside the body, Sotomayor came back.

“So what's the difference? I mean, if you cut off a piece of the whole in the kidney or liver, you're saying that's not patentable,” she said. “But you take a gene and snip off a piece, that is?”

Castanias eventually got across the point that one could not get a patent on a kidney or liver, but really because Section 103 on obviousness “does this work better than Section 101.”

“That's very, very interesting,” Breyer said. He accused Castanias of casting Section 101 so broad as to allow patenting of “anything under the sun,” a phrase used in Chakrabarty and on which many of the briefs in this case relied. Putting a pin in that bubble, Breyer said, “it seems to me, we've rejected [the anything-under-the-sun view of Section 101] more often than we've followed it.”

“And particularly with a thing found in nature doctrine,” he continued. “Everything is inside something else. Plants, rocks, whatever you want. And so everything will involve your vast taking something out of some other thing where it is, if only the environment.”

Verrilli: Double-Edged Sword of Patent Law

Verrilli took the position in between the two parties, both figuratively and in order at oral argument. At the Federal Circuit and in its brief with the high court, the government has compared patent eligible cDNA claims and ineligible isolated DNA claims by saying the former are “synthetic molecules built by scientists” and the latter are “isolated but otherwise unmodified human genomic DNA.”

Verrilli began to express that view in court but immediately ran into a question posed by Sotomayor: “Are you fighting over nothing? If [Myriad] can patent this cDNA in the way they have, what does it matter [if Myriad cannot patent isolated genomic DNA]?”

Sotomayor's question was whether researchers would be able to do anything meaningful with the isolated genomic DNA should the court determine it was not patent eligible.

The ACLU's Hansen initially said that much of today's work on recombinant DNA would be equally obliged to proceed under a patent license if the cDNA claims were upheld, but Verrilli said that was not his understanding.

When Kennedy asked Verrilli to suppose it were true, though, the solicitor general still maintained that cDNA was man-made and so would be patent eligible.

Isolated vs. cDNA: Can Section 101 Be a Threshold?

Chief Justice John G. Roberts Jr. was not pleased that the government thus wanted the court to set a threshold like that under Section 101.

“I thought the basic general approach here was we have a very expansive view of what is patent eligible and then we narrow things through things like obviousness and so on,” he said. “Why wouldn't it make more sense to address the questions at issue here in the obviousness realm?”

Verrilli contended that the court's position in Mayo provided the answer. In Mayo, he said,  

the Court recognized that the threshold test under Section 101 for patent eligibility does do work that the obviousness test and a novelty test and a specification test do not do; and the work that it does here, I would respectfully submit, is to ensure that the natural substance, the product of nature itself, is not subjected effectively to a monopoly, because if it can be deemed to be a human invention solely as a result of the change that occurs when you extract it from the body, then that means, as a practical matter that you have granted a patent on the gene itself because no one else can extract it because extracting it is isolating it; isolating it violates the patent. And so as a result of that, no one else can try to develop competing tests for breast cancer, no one else can try to use this gene for recombinant DNA.  





Roberts said the answer was nonresponsive to distinguishing patent eligibility and obviousness, but Verrilli insisted that Mayo held that “the right answer to that question … is to focus on them at the eligibility stage, because getting the balance right is of critical importance.”

Alito now joined Roberts in criticizing the ACLU and the government for wanting such a broad result. Again, Verrilli pointed back “to what the Court said last term in Mayo, which is that the determination of patent eligibility really is a double-edged sword.”

“The proposition of whether you can patent the gene itself is a question we think of fundamental importance,” he said, “and it raises exactly the two-edged sword concern that led the Court to conclude what it did in Mayo.”

Preemption Permeates Discussion

The “two edges” Verrilli was referring to are rewarding innovation with a patent property right compared to preempting follow-on innovation with patent claims that should be excepted from the broad categories.

In recent briefs and now at oral argument, Myriad appeared to be backing away from its early history of threatening to sue researchers and claiming anything more than the composition of matter itself--and not the informational content of the isolated DNA.

“These [claims] are for specific molecules that exist in the physical world,” Castanias said in court. “There is no risk of anything being preempted other than what the claims properly claim, which are human-made inventions of isolated molecules.”

Hansen disagreed.

“People can't use pieces of the BRCA gene to recombine them and find new treatments and find new diagnoses and find new things that will advance medicine and science as a result of these patents,” he said. “It's a perfect example of what the point of the product of nature doctrine is.”

But Will Scientists Invest in Innovation?

Justice Antonin Scalia said that response missed the point, in that the identification of the relevant isolated DNA comes first. He echoed a concern that Kagan had expressed earlier.

“What advantage do I get from being the person or the company that isolated that gene,” he said to Hansen. “You say none at all.”

“No, I think you get enormous recognition,” Hansen said, but Scalia cut him off before he could go further.

“Well, that's lovely,” he said.

But the question remained whether the incentive has to exist for discovering isolated DNA or whether the incentive of a patent on cDNA would be sufficient to encourage investment.

Sotomayor asked, “Is there some value to us striking down isolated DNA and upholding the cDNA? If we were to do what the government is proposing in this case, what's the consequences?”

Hansen appeared to miss the question, as he said the value in such a decision would be to uphold the product of nature doctrine, but he made no distinction between the two types of claims.

Does Isolated DNA Exist in Human Body?

Sotomayor had a concern with other claims that have not been the focus to date, but she argued were controversial because they were drawn to 15 nucleotides only. The process of isolation removes portions of the nucleotide sequence but not so much that the 15 nucleotides would reasonably be found in the human body, which according to Sotomayor would again defy Myriad's claim to a difference with genomic DNA.

However, the claims in question are cDNA claims, which she was already assuming were man-made.

The court also seriously considered a question raised in an amicus brief by Eric S. Lander, a geneticist and molecular biologist involved in the Human Genome Project. Lander maintained that, because of the way portions of cells die within the human body, isolated DNA in precisely the sequences claimed by Myriad's patents can occur, albeit probabilistically--not by observation.

If so, that could be seen to cut against Myriad's argument that its scientists had to perform creative manipulation to discover sequences with no counterparts in the human body..

Alito would have none of that argument. One of the other analogies often made during this case has been that of a baseball bat. The argument is that a baseball bat is patent eligible even if the tree branch from which it is shaped is not.

Alito envisioned that at some time and “possibly someplace a branch has fallen off a tree, and it's fallen into the ocean, and it's been manipulated by the waves, and then something's been washed up on the shore, and what do you know, it's a baseball bat.”

But How Much Manipulation Is Enough?

Castanias appreciated Alito's defense, but the word “manipulated” came up often in the discussion, and it seemed to trip up both Castanias and Hansen.

Hansen, trying to make the case against cDNA, said there was some manipulation, but that “it's letting nature manipulate, not the scientist manipulating.”

That did not impress Scalia.

“You've really lost me when you say that it's nature that does the alteration rather than the scientist,” he said. “I mean, whenever a scientist does an alteration, he does it, you know, by some force of nature. I mean, he doesn't do it unnaturally, does he?”

Castanias, for his part, talked about the actual task of creating the molecule claimed in the isolated DNA claims, but Roberts could not see how that was more than just “snipping along a line.” And Kagan treated Castanias's argument as merely pointing to the effort and ingenuity it takes to find the right place to snip.

Returning to the Amazon plant analogy, Kagan asked, “Are you saying that you could patent that plant because it takes a lot of effort and a lot of ingenuity to find it?”

Castanias recast the patent eligible part of the plant in terms of the extraction, and he called that manipulation, but Kagan did not agree.

“I mean, I don't know what manipulation means,” she said. “I mean, you have to take the plant and uproot it, all right?”

Castanias said he did not think of patent-eligible extraction in the sense of “[a]ll I have done is isolate the plant from the forest.” However, he continued to claim that much more was at issue with what Myriad's scientists did. And he ultimately rejected the idea that the degree of manipulation could provide any kind of dividing line on patent eligibility.

“What you will then be asking litigants to do and courts to do is to draw fine distinctions under Section 101 between, well, how much more manipulation” confers patent eligibility, he said.

Going Beyond This Case

In the same context, Castanias cautioned that the court seemed to be extending the product of nature doctrine too broadly, in the face of other scientific advances.

“Modern medicine, particularly the area of personalized medicine, is trying to get to a point where what we are administering to individual patients is giving them the opportunity to mimic the actions of the body,” he said. “And so, actually, the goal of medicine is to get closer to nature, rather than farther away. And anything that takes the product of nature doctrine beyond the simple truism that the product of nature is something that is not a human invention, then that's very dangerous, not just for our case.”

But Kennedy turned that admission against Castanias by distinguishing Myriad's claims to probes and primers from those directed to the isolated DNA. That distinction also cut against Myriad in the context of its argument that isolated DNA is different from what is in the body in that, according to Myriad, what is in the body cannot be used in any diagnostic sense.

“Your answer was not quite accurate when you said, well, it can't be used in the body to detect breast cancer,” Kennedy said. “Neither can the isolate without some additions.”

That was perhaps what most impressed Bracewell & Giuliani's Samardzija, who agreed that the court may well reject the isolated DNA claims but only those.

“The court really got the point of personalized medicine,” he told BNA. “If all of a sudden those claims are not patent eligible, that's going to be a problem.”

By Tony Dutra  

Unofficial transcript is available at http://www.supremecourt.gov/oral_arguments/argument_transcripts/12-398-amc7.pdf.

Text of Myriad's brief is available at http://pub.bna.com/ptcj/120398Myriad13Mar11.pdf.

Text of the petitioners' brief is available at http://pub.bna.com/ptcj/120398ACLU13Jan23.pdf.

Text of the government's brief is available at http://pub.bna.com/ptcj/120398US.pdf.

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