For the half-year to 31 December 2014, the IPKat's regular team is supplemented by contributions from guest bloggers Rebecca Gulbul, Lucas Michels and Marie-Andrée Weiss.

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Wednesday, 17 April 2013

Patentability of DNA sequences: the debate before the US Supreme Court

Counting sheep is usually regarded as a useful aid to fall asleep. Most people would agree that reading lengthy judgments, or overly-complicated scholarly papers, can be as helpful as counting sheep to drift off. But an IP-driven creature, like the IPKat, reacts in the opposite way: the excitement and thrill of discovering something new to report to his readers keep him awake through the night. This is exactly what happened yesterday evening/night to this Kat, who came across a transcript of the oral arguments heard on Monday before the US Supreme Court, in the important case Association for Molecular Pathology v Myriad Genetics. Needless to say, he could not resist the temptation to devour it and let readers know what was discussed before the Supreme Court.

The current composition of the US Supreme Court
Although the case is certainly familiar to many readers, a brief summary is due. At issue is the patentability of isolated DNA sequences, in particular in relation to diagnostic and drug screening claims. Myriad Genetics, a spin-off from the University of Utah's Centre for Genetic Epidemiology, holds several patents which cover two genes associated with an increased risk of breast and ovarian cancer, BRCA1 and BRCA2 (together with their mutations and cDNA - DNA synthesised by mRNA, through a process which removes non-coding sequences, called introns), as well as the methods to detect their entire sequence and mutations, and the associated diagnostic tests and screening procedures (claims 1, 2, 5, 6, 7, and 20 of US patent 5,747,282; claims 1, 6, and 7 of US patent 5,837,492; claim 1 of U.S. patent 5,693,473; claim 1 of U.S. patent 5,709,999; claim 1 of US patent 5,710,001; claim 1 of US patent 5,753,441; claims 1 and 2 of US patent 6,033,857). The company provides expensive diagnostic tests based on the patented isolated DNA sequences (denominated BRACAnalysis) and actively tried to stop competing laboratories from performing unlicensed BRAC tests (cease and desist letters were sent, inter alia, to the Genetics and IVF Institute and the University of Pennsylvania's Genetic Diagnostic Laboratory in 1998 (head here for a more detailed account of the facts that gave rise to the case).

The Association for Molecular Pathology (and other plaintiffs) sued Myriad, seeking invalidation of the contested claims. AMP asserted that the claims covered products of nature, laws of nature, natural phenomena, abstract ideas or basic human knowledge, disputing the subject matter's patentability, in light of 35 U.S.C. §101. Further, it argued that the patents hindered scientific research and innovation, prevented competition and threatened patients' rights. Myriad relied on the USPTO's practice, which expressly recognised the patentability of isolated DNA sequences, and claimed that the isolation process resulted in a transformation which rendered the matter patentable. On March 29, 2010, the District Court for the Southern District of New York declared the contested claims invalid, observing that, 'because the claimed isolated DNA is not markedly different from native DNA as it exists in nature, it constitutes unpatentable subject matter under 35 U.S.C. § 101', reaching the same result with regard to the method of comparison of DNA sequences, deemed to be an non-patentable abstract mental process.

On appeal (as reported by the IPKat here), the US Court of Appeals for the Federal Circuit overturned the District Court's decision in part, ruling that both isolated DNA sequences and cDNA, as well as the claimed screening method (which implied assessing potential cancer therapeutics via changes in cell growth rates) were patentable subject-matter (only the method of comparison of DNA sequences was deemed invalid). The Court of Appeals also observed that the patentability of DNA sequences comported with the long-standing practice of the USPTO, adding that:
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. It is the difference between knowledge of nature and reducing a portion of nature to concrete form, the latter activity being what the patent laws seek to encourage and protect. The government’s microscope could focus in on a claimed portion of any complex molecule, rendering that claimed portion patent ineligible, even though that portion never exists as a separate molecule in the body or anywhere else in nature, and may have an entirely different utility. That would discourage innovation. ... Visualization does not cleave and isolate the particular DNA; that is the act of human invention.
What happened to my DNA?
A writ of certiorari was granted by the Supreme Court, which vacated the Court of Appeal's decision, remanding the case for re-evaluation, in light of Mayo Collaborative Services v Prometheus Laboratories Inc. The Federal Circuit, on August 16, 2012, essentially upheld its previous judgment (IPKat's comment here). A second petition for certiorari was then filed with the Supreme Court in September 2012. On Monday, April 15, the Court heard oral arguments, which this Kat briefly summarises below (Mr. Hansen spoke on behalf of the petitioners; General Verrilli on behalf of the United States as amicus curiae; Mr. Castanias on behalf of the respondents).
  • Is the isolation or extraction of natural products patentable?
Justices Alito and Ginsburg focused on the patentability of natural products, which are isolated or extracted through methods involving human intervention. For example, Justice Alito said (reflecting on the petitioners' arguments):
Suppose there is a substance, a chemical, a molecule in the leaves of a plant that grows in the Amazon, and it's discovered that this has tremendous medicinal purposes. Let's say it treats breast cancer. A new discovery, a new way is found, previously unknown, to extract that. You make a drug out of that. Your answer is that cannot be patented; it's not eligible for patenting, because the chemical composition of the drug is the same as the chemical that exists in the leaves of the plant.
Mr. Hansen replied that '[i]f there is no alteration, if we simply pick the leaf off of the tree and swallow it and it has some additional value, then I think it is not patentable'. He added that it may be possible to obtain a method patent on it, but not a composition patent, as 'finding a new use for a product of nature, if you don't change the product of nature' does not make the latter patentable.

Justice Sotomayor posed a tricky question to Mr. Castanias:
I have a sort of analytical problem. I find it very, very difficult to conceive how you can patent a sequential numbering system by nature, in the same way that I have a problem in thinking that someone could get a patent on the computer binary code merely because they throw a certain number of things on a piece of paper in a certain order. I always thought that to have a patent you had to take something and add to what nature does. So how do you add to nature when all you are doing is copying its sequences?
Mr. Castanias answered that 'there was invention in the decision of where to begin the gene and where to end' it. He also recited 35 U.S.C. §103, which states that '[p]atentability shall not be negated by the manner in which the invention was made' and made ample reference to the USPTO practice and guidelines (in particular, §2107). The respondent focused on the fact that inventive human intervention is needed to identify, extract and use genes, even though they are a naturally occurring substance. 'The goal of medicine', Mr. Castanias added, 'is to get closer to nature, rather than farther away'. Thus, '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...'.

Justice Kagan asked Mr. Castanias whether he considered chromosomes to be patentable. The cunning trap was set and Justices Kagan and Sotomayor got to a much more dangerous question (and Justice Breyer showed similar concerns, in relation to the requirements set by §101):
So, you know, if not the more 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? (Justice Kagan)
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, but you take a gene and snip off a piece, that is? (Justice Sotomayor)
Mr. Castanias cited the Chakrabarty case to argue that §101 should be interpreted broadly. Justice Breyer noted that such a broad understanding would lead to the eligibility of 'anything under the sun'.
  • Are there sufficient incentives for genetic research, if genes are non-patentable?
The Court appeared concerned with the possible consequences that a decision excluding the patentability of DNA sequences would yield on research and innovation. Justice Kagan set out the question:
If you assume that it takes a lot of work and takes a lot of investment to identify this gene, but the gene is not changed in composition, and what you just said is that discovering uses for that gene would not be patentable even if those uses are new, what does Myriad get out of this deal? Why shouldn't we worry that Myriad or companies like it will just say, well, you know, we're not going to do this work anymore?
Mr. Hansen's elusive answers (which pointed to public financing, curiosity, enormous recognition, Nobel prizes) appeared not to please the Court. But Justice Sotomayor accepted the idea that the prospect of obtaining a process or development patent may still fuel research in this field.

Chief Justice Roberts discussed with General Verrilli about the distinction between eligibility requirements and issues of obviousness: the Solicitor General made references to Mayo Collaborative Services and Diamond v ChakrabartyJustice Alito wondered if focusing on the eligibility stage would be the best solution:
Why should we [focus on §101]? We have claims that if patent eligibility is denied here it will prevent investments that are necessary for the development of new drugs or it will lead those who develop the new drugs, new diagnostic techniques, to keep those secret, not disclose them to the public. Why should we jump in and decide the broadest possible question?
General Verrilli observed that in Germany and France it is possible to obtain patents on isolated genomic DNA only for a particular use. He suggested that a similar solution would yield an optimal result, preserving research on non-patentable genes, but allowing use patents, which secure the recoupment of research investments.

Justice Kennedy asked Mr. Castanias if a decision accepting the patentability of cDNA, and rejecting that of DNA sequences, would 'give the industry sufficient protection for innovation and research'. The respondent somehow evaded the answer, focusing instead on the utility guidelines and on the manipulation that occurs when isolating DNA: this is similar, according to Mr. Castanias, to what happens in relation to other molecules which are peacefully considered patentable.
  • Differences between DNA and cDNA
A considerable amount of questions concerned the role and function of cDNA. The Court appeared more open to the patentability of cDNA than to that of isolated natural DNA sequences. Justice Sotomayor expressly stated that cDNA is a product of human invention and wondered if the petitioner was really challenging patentability or, instead, obviousness. Justice Ginsburg similarly observed that cDNA appears to involve manipulation.

Mr. Hansen focused on the process through which cDNA is made, noting that, although manipulation does occur, 'it's letting nature manipulate, not the scientists'. He pointed to the differences between the processes that allow the production of cDNA and aspirin: only the latter results in an alteration of the function of the natural substance, as cDNA and DNA, instead, have exactly the same function.

General Verrilli provided an overview of the distinction between DNA and cDNA and the possible consequences of their patentability:
The claim that isolated DNA is a human invention rests entirely on the fact that it is no longer connected at the molecular level to what surrounded it in the body. But allowing a patent on that basis would effectively preempt anyone else from using the gene itself for any medical or scientific purpose. That is not true about a patent on cDNA. A patent on cDNA leaves the isolated DNA available for other scientists and others in the medical profession to try to generate new uses.
The oral arguments offered an occasion to perceive the general orientation of the Supreme Court. It appears that judges were not particularly persuaded by arguments pointing to the patentability of isolated DNA sequences, whereas they exhibited higher sensitivity towards the patentability of cDNA, as suggested by the US Government. The decision is expected by the end of June, but a reasonable guess is that focusing on patents that protect methods, processes and uses, as suggested by Justice Sotomayor, might be the key to guarantee equal protection to all the interests at stake.

6 comments:

Anonymous said...

I cannot understand why, all of a sudden, gene patents would be invalid. Haven't they been granted for like 20 years? Is this a massive policy change? If so, who would be liable for the damages Myriad would have to bear? The US Government? And what's going to happen to the other thousands gene patents? And to the equivalent patents granted, for example, by the EPO?
It's temporary, but absolute protection. I'd say deal with it till it's over and then everyone can play with it. We don't need to fix something that is not broken!

Anonymous said...

Thanks for this neat digest, easier to read than 80 pages of transcript before bedtime. One issue bothers me: if the SCOTUS rejects the patentability of DNA sequences, what happens to genetic research? The plaintiff apparently said that a use patent is enough to drive the investments involved in biotech R&D. Fine, but we should keep in mind that we are talking about huge investments, which span over many years, if not decades, and involve hundreds of researchers, just to identify sequences. Then you have to add other years of research and experimentation to create drugs or screening tests. Perhaps, allowing a company to recover part of its research investments before the second stage is completed would actually lower the cost, for the end user, of the final product. Thinking of something like a RAND commitment or a research exemption. Just my 2 cents!

Anonymous said...

"The plaintiff apparently said that a use patent is enough"
But THERE ARE NO USE PATENTS IN THE US!
They are held invalid. One has to get "methods of treatment" NOT use of X as a medicament...

hollyipltd said...

One of the problems with product claims to human genes is that by demonstrating a single industrial applicability one has a monopoly for all their uses even though they are yet to be identified. From what I understand infringement in France and Germany of such product claims to genes would only be found if the party was somehow taking advantage of the use/function disclosed in the patent. That seems a fair way of dealing with the issue, and I hope the US Supreme Court will find its way to a similar solution.

Anonymous said...

"From what I understand infringement in France and Germany of such product claims to genes would only be found if the party was somehow taking advantage of the use/function disclosed in the patent. "


This is true for all UE countries.

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:62008J0428:EN:HTML

Rahul said...

A very good brief on the issue by Stefano.

Further, the various analogies made by the Hon'ble judges weren't really impressive. They were largely comparing oranges and apples.

I do not buy the argument that the isolated chemical substances have same "functions" as that of the same substance found in natural sources. I would give the reason why. The reason is that when in natural sources, the chemical substance serves the function with regards to enhancing properties of its natural source. In case of genes, they serve the "function" of passing genetic information and coding proteins for normal or "abnormal" functioning of cells. When isolated, the DNA sequences have different "function". They "function" as therapeutic or a diagnostic agent,which they cannot do when in their natural sources.

On the basis of above definition of "function", even isolated DNA sequences are due to human intervention, just like cDNAs. Today, if biotech industry surrenders the idea of patentability of isolated DNA sequences, tomorrow the civil unions will subvert patentability of cDNA on basis of "obviousness" or lack of inventive step.

I think the industry must hold strong onto its arguments in this case. There is no middle path like just sticking to method claims or just sticking to cDNA claims.

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