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Cancer, Genetics, In the News, Medicine and Society, Science, Science Policy

How will the Myriad decision affect patient care? Stanford experts comment

How will the Myriad decision affect patient care? Stanford experts comment

I recently had the opportunity to talk in-depth with Stanford clinicians and faculty members about how the U.S. Supreme Court decision on the Myriad gene-patenting case may affect patient care. The answer? Surprisingly little (at least in near future). That’s in part due to the large proprietary database of BRCA mutations amassed by the company. As I wrote in my article:

…Although the ruling may be an ethical and philosophical triumph for those who believe that human genetic information should not be claimed by any corporate entity for profit, it’s not likely that patient care will change immediately, according to breast cancer clinicians at the Stanford Cancer Institute. Myriad’s experience in the field of BRCA gene testing and interpretation will be difficult to surpass, at least for a while, they said. Over time, however, the ruling should result in a freer research atmosphere that will translate into improvements for patients.

The piece includes the thoughts of leaders of the Stanford Cancer Institute, the institute’s breast oncology and molecular therapeutics program, big data experts and bioethicists. I hope you enjoy reading it as much as I enjoyed writing it!

Previously: Reaction on gene-patenting ruling from around the web, A closer look at Supreme Court’s decision on gene patenting and Examining how the Supreme Court ruling on gene patenting affects medical and scientific research

Cancer, Genetics, In the News, Medicine and Society, Science, Science Policy

Takeaways from last week’s gene patenting decision

Takeaways from last week's gene patenting decision

Maybe, like me, you read everything you could get your eyes on last week about the gene patenting case, and spent several days pondering the implications of the ruling by the Supreme Court that companies like Myriad Genetics can’t patent isolated human genes. Or, maybe you’re a busy person with not much time to dive deeply into the issue. If so, you might find today’s summary by the National Geographic - 7 Takeaways from Supreme Court’s Gene Patent Decision – a useful primer.

The article quotes Jake Sherkow, JD, and Hank Greely, JD, from the Stanford Center for the Law and Biosciences, who each provided comment on the case for us and other members of the media last week. I found point 2 – “Synthetic DNA is fair game” – to be particularly interesting, since it’s one of the first discussions of what the ruling allows, rather than prohibits:

While companies can no longer patent genes with the same sequences found in cells, the decision allows edited forms of genes not found in nature—known as complementary DNA, or cDNA—to be patented.

cDNA is not useful for diagnostic tests, but it is crucial for producing protein-based drugs, explained Robert Cook-Deegan, a professor of genome ethics, law, and policy at Duke University’s Institute for Genome Sciences and Policy.

“Those are the billion-dollar molecule patents,” Cook-Deegan said. “Biotech companies care a great deal about cDNA patents, and it should be reassuring to them that those patents are still fine.”

Hank Greely, a bioethicist and law professor at Stanford University, predicts cDNA patents will become even more valuable as scientists move beyond merely exploiting naturally occurring proteins.

“In the longer run, as we move into an era of synthetic biology, where we start trying to improve upon nature, then I think [cDNA patents] will be important,” Greely said.

Previously: A closer look at Supreme Court’s decision on gene patenting, Supreme Court rules on Myriad’s “gene patenting” case and Are genes patentable? A summary of the Supreme Court case

Cancer, Genetics, Medicine and Society, Research, Science, Science Policy

Examining how the Supreme Court ruling on gene patenting affects medical and scientific research

Yesterday’s Supreme Court ruling declaring that isolated genomic DNA is not eligible for patent protection, but that cDNA – “cloned” or “complementary DNA” – can be patented ignited a frenzy of news stories and commentaries about the decision. In a segment on KQED’s Forum this morning, Mildred Cho, PhD, associate director of the Stanford Center for Biomedical Ethics and a professor of pediatrics,  joined the discussion on how the ruling will affect medical and science research. Listen to the full discussion here.

Previously: A closer look at Supreme Court’s decision on gene patenting and Supreme Court rules on Myriad’s “gene patenting” case

Cancer, Genetics, In the News, Medicine and Society, Science, Science Policy

Reaction on gene-patenting ruling from around the web

Reaction on gene-patenting ruling from around the web

Wow, what a busy day for gene patenting discussions! This morning’s decision (.pdf) by the Supreme Court that isolated DNA is not patentable has sparked a wave of stories, press releases and announcements across the web. I thought I’d pull together some of the most useful information I’ve found today on the topic.

Twitter provided a forum for immediate responses to the ruling, my favorite of which was authored by NIH director Francis Collins, MD, PhD:

(Collins later followed-up with a much more staid official statement, but I still love the “Woo hoo.”) The Twitter feed from the National Human Genome Research Institute was only a bit more restrained:

Several Stanford experts weighed in as well, including Stanford law professor and bioethicist Hank Greely, JD, who had a slightly different reaction to the ruling:

Geneticist Carlos Bustamante, PhD, also tweeted his thoughts about the issue of consumer choice (scroll down to read tweet series).

As the day wore on, it became apparent that those on both sides of the issue were claiming a victory of sorts. Myriad issued a positively worded release highlighting the Court’s decision to uphold the company’s cDNA patents. Stock in Myriad (and other biotechnology companies) initially jumped after the announcement, but ended the day down about 5.6 percent.

Two genetic testing companies (Ambry Genetics and Gene by Gene, Ltd) that I know of (there could well be more) jumped into the fray this afternoon with announcements that they will immediately begin offering BRCA1 and BRCA2 testing to patients at prices much lower than the $3,000 to $4,000 charged by Myriad. It remains to be seen, however, how much of an advantage Myriad’s proprietary database (used to interpret the sequence results and deliver risk estimates to patients) will confer to savvy patients who may choose to pay a premium for access to this cloistered information. Personally, I’m really interested in the effect the ruling will have on an end-around effort by researchers trying to reconstitute Myriad’s database by compiling individual patient’s reports from the company.

Finally (for now), for a general overview of the history of BRCA gene patenting and the field of genetic testing, check out this excellent article from Nova Next. I have a feeling I’m going to be reading it more than once as I (along with many experts in both law and biology) puzzle through the issues for these next few days and weeks.

Previously: A closer look at Supreme Court’s decision on gene patenting, Supreme Court rules on Myriad’s “gene patenting” case and Are genes patentable? A summary of the Supreme Court case

Cancer, Genetics, Medicine and Society, Science, Science Policy

A closer look at Supreme Court’s decision on gene patenting

A closer look at Supreme Court's decision on gene patenting

As previously discussed here and elsewhere, the Supreme Court today issued its opinion in the gene patenting case Association for Molecular Pathology vs. Myriad Genetics, Inc. In a unanimous decision (.pdf) authored by Justice Thomas, the Court declared that isolated genomic DNA was not eligible for patent protection, but that cDNA – “cloned” or “complementary DNA” – could be patented. This was largely the outcome some predicted after oral argument. And while the actual business and research effects of the decision remain to be seen, this does bring to a close the longstanding practice of patenting isolated portions of the human genome in its native state.

This likely brings to a close Myriad Genetics’ saga of aggressively enforcing its patents directed to BRCA1 and BRCA2 testing

The Court’s decision was relatively simple. It began with a largely accurate, and lengthy, recitation of the molecular biology behind transcription and translation. This factored significantly into the Court’s discussion of the differences between isolated genomic DNA and cDNA, particularly the absence of introns from cDNA molecules. It then assessed the patents’ claims at issue, which were generally directed to “an isolated DNA” of varying lengths and sequences. The opinion noted that, “Myriad’s patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes… by breaking the covalent bonds that connect the DNA to the rest of the individual’s genome.” And the Court concluded its opinion by declaring that claims directed to molecules of isolated genomic DNA, themselves, were unpatentable “products of nature” because Myriad did not “alter any of the genetic information encoded in the BRCA1 and BRCA2 genes,” nor did the isolated genomic DNA possess “markedly different characteristics from any found in nature.”

The Court rejected Myriad’s claim that it created a new chemical entity because, in isolating the genes from their surrounding chromosomes, Myriad necessarily cleaved the chemical bonds of the chromosomes’ phosphate backbones. This was irrelevant because “Myriad’s claims are simply not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA.”

As for Myriad’s cDNA claims, however, the Court – in a single, short paragraph – declared them eligible for patent protection because the “non-coding regions have been removed,” thus creating a new molecule not found in nature. Interestingly, the Court recognized the possibility of retrovirii potentially creating identical DNA transcripts to the cDNAs at issue, but dismissed this concern in a footnote: “The possibility that an unusual and rare phenomenon might randomly create a molecule similar to one created synthetically through human ingenuity does not render a composition of matter nonpatentable.”

Bizarrely, Justice Scalia joined the Court’s opinion in its entirety except for its preliminary scientific discussion. In a separate concurrence, Justice Scalia wrote: “I am unable to affirm those details on my own knowledge or even my own belief.” Typically, Justice Scalia does not qualify the factual portions of opinions he joins, even where they involve science. And notably, in the Court’s recent decision in Maryland v. King involving the constitutionality of warrantless DNA tests for arrestees, Justice Scalia’s dissent is replete with the factual differences between DNA and fingerprint testing.

This likely brings to a close Myriad Genetics’ saga of aggressively enforcing its patents directed to BRCA1 and BRCA2 testing. Myriad will continue to offer its BRACAnalysis product, which, because of its trade secret mutational database, is likely still the most robust BRCA test on the market. And competitors will be able to enter the BRCA testing market and make use of Myriad’s methods, although they will have to do so without the benefit of certain cDNA molecules or Myriad’s clinical data.

But the decision leaves a number of legal questions unanswered: What about other patents directed to “isolated and purified” natural products? Are cDNAs nonetheless obvious, and therefore unpatentable for that reason? And, considering the Court’s mention of retrovirii, how “unusual and rare” must a “natural phenomena” be to still be patent eligible if synthetically created? These are issues that the lower courts are likely to struggle with going forward, and issues that may, one day, be back in the hands of the Supreme Court.

Jake Sherkow, JD, is a fellow at Stanford Law School’s Center for Law and the Biosciences. His current research focuses on the intersection of patent law, biotechnology, and agency regulation.

Previously: Supreme Court rules on Myriad’s “gene patenting” case and Are genes patentable? A summary of the Supreme Court case

Cancer, Genetics, In the News, Medicine and Society, Science, Science Policy

Supreme Court rules on Myriad’s “gene patenting” case

Supreme Court rules on Myriad's "gene patenting" case

This morning, the U.S. Supreme Court issued their anxiously awaited decision in the case of the Association for Molecular Pathology vs. Myriad Genetics, Inc. Often called the gene patenting case, the case raises the issue of whether companies like Salt Lake City-based Myriad Genetics, Inc. can patent genes, in this case, the BRCA1 and BRCA2 genes. Mutations in these genes confer a substantially higher risk of breast or ovarian cancer.

The Court ruled that naturally isolated DNA is not patentable, but that synthetic DNA (such as the cDNA for the BRCA1 and 2 genes) is patentable. The decision was unanimous. From the decision:

A naturally occurring DNA segment is a product of nature and not patent eligible merely becauseit has been isolated, but cDNA is patent eligible because it is not naturally occurring.

cDNA is not a “product of nature,” so it is patent eligible under §101. cDNA does not present the same obstacles to patentability as naturally occurring, isolated DNA segments. Its creation results in an exons-only molecule, which is not naturally occurring. Its order of the exons may be dictated by nature, but the lab technician unquestionably creates something new when introns are removed from a DNA sequence to make cDNA.

We’ll have a longer comment about the decision later today or tomorrow from Jacob Sherkow, JD, a fellow at Stanford Law School’s Center for Law and the Biosciences. Sherkow recently wrote a wonderful blog post for us summarizing the oral arguments in the case, which took place in April. And the SCOTUS blog carried a great, ‘made simple’ synopsis of the issue earlier this year for readers who want to quickly get up to speed.

The decision is likely to have far-reaching implications for the many other gene patents granted by the U.S. Patent and Trademark Office since the first gene (chorionic somatomammotropin) was patented by the University of California, Berkeley, in the early 1980s. The National Society of Genetic Counselors now estimate that around 20 percent of all human genes are patented.

Previously: Are genes patentable? A summary of the Supreme Court case, At Stanford event, cancer advocate Susan Love talks about “A future with no breast cancer” and BRCA patients use Stanford-developed online tool to better understand treatment options
Photo by Mark Fischer

Ethics, NIH, Patient Care, Pediatrics, Research, Science Policy

Bioethicists say criticisms of preemie oxygen study could have “chilling effect” on clinical research

Bioethicists say criticisms of preemie oxygen study could have “chilling effect” on clinical research

Thanks to a public outcry that included objections from bioethics experts from across the country, the federal Office for Human Research Protections (OHRP) has decided to suspend sanctions it imposed earlier this year on a study of blood oxygen levels used to treat premature infants. The OHRP’s sanctions, issued in March, sharply criticized the study’s leaders for not providing the infants’ parents with adequate information about the risks of the trial. But many bioethics experts disagreed with the OHRP’s assessment of the situation.

Last week, a group of more than 40 of the country’s top bioethicists, including two at Stanford, sent a letter to OHRP stating that the sanctions could have a chilling effect on much-needed clinical research. In a highly unusual action, Francis Collins, MD, PhD, the director of the National Institutes of Health, worked with two colleagues to write a similarly critical letter that said, in part:

This controversy has alarmed some of the parents of infants who were in the study, confused the biomedical research community, and befuddled IRBs. Several other studies seeking new insights to improve care for these vulnerable infants have been put on hold as the field tries to understand the OHRP findings.

The two letters appear online today in the New England Journal of Medicine (NEJM), and constitute a remarkably intense criticism of the OHRP, the agency within the U.S. Department of Health and Human Services responsible for overseeing the safety and well-being of human research subjects.

I’ve been following the developing story with the help of Stanford bioethicist David Magnus, PhD, who was one of the writers of the bioethicists’ letter. Last week, before the agency revised its stance, Magnus summarized what the bioethics community found objectionable about the OHRP’s sanctions: “They believe in an absolute interpretation of risk,” he said. The agency’s risk assessment was based “not [on] what kids who are actually sick would be exposed to, but what a healthy child would be exposed to.” Healthy babies born at term face much lower risks of severe eye disease, neurological damage and death than the babies in the study – but the tiny preemies in the study weren’t healthy term infants, and were not placed at additional risk, the bioethicists assert, because of their participation in the study.

The tussle has a complex back story that involves 1,300 fragile premature infants, their parents, 23 academic medical centers and an important piece of paperwork.

Continue Reading »

NIH, Research, Science, Science Policy

Shortfall of physician-scientists: “A national concern”

Shortfall of physician-scientists: "A national concern"

The importance of the physician-scientist is the focus of a new Perspective piece in the New England Journal of Medicine. Writing that an increasing number of MDs have moved away from the laboratory and into clinical practice, and calling the shortfall of new physician-researchers a “national, if not global, concern,” Michael M. Gottesman, MD, outlines how the National Institutes of Health is working to reverse the trend. And he notes that the awarding of the 2012 Nobel Prize in Chemistry (which went to Robert Lefkowitz, MD, and Stanford’s Brian Kobilka, MD, both trained in cardiology) “should remind us of the critical role that clinician-scientists have played in formulating the seminal concepts that govern modern biomedical science.”

Previously: Funding basic science leads to clinical discoveries, eventually, Why basic research is the venture capital of the biomedical world, At press conference, Nobel Laureate Brian Kobilka discusses his research and “irrational optimism” and Stanford’s Brian Kobilka wins 2012 Nobel Prize in Chemistry

Genetics, In the News, Medicine and Society, Science, Science Policy

Are genes patentable? A summary of the Supreme Court case

Are genes patentable? A summary of the Supreme Court case

As you likely heard, the Supreme Court heard oral arguments yesterday in a case that’s of interest to many biomedical researchers. That case, widely known as the “gene patenting case,” has a single question presented: “Are human genes patentable?” It may irk some researchers and clinicians that the answer isn’t a straightforward “no.” But the issues are surprisingly complex: How does one define a “gene,” and a “human” vs. a “synthetic” one at that? What about primers, probes, and cDNA? And what does one mean by “patentable”?

First, a brief lay of the legal landscape. Typically, an inventor cannot patent a “product of nature.” But ever since a 1911 appellate decision (.pdf), a natural product can be patented if it’s “isolated and purified” from its surrounding environment. Thus, the chemical compound adrenaline was itself patented because it was isolated and purified from adrenal glands. Shockingly, the Supreme Court has never directly reviewed this isolated and purified doctrine, even after 102 years.

This all raises the question of whether human genes should be allowed to be patented as a matter of policy, if not law.

And so, on this basis, isolated human genes have long been patented. In 1994, researchers at the University of Utah finally located and sequenced (.pdf) the BRCA-1 and BRCA-2 genes, variants of which put women at astonishingly high risk for early onset breast and ovarian cancer. Those researchers obtained patents on both the isolated sequences and cDNA variants of those, and assigned them to Myriad Genetics, a diagnostic testing company.

Arguments at the Supreme Court - and the justices themselves – grappled with the distinctions between isolated genomic DNA and cDNA. Lower court opinions had made a significant case out of the fact that because the covalent bonds of isolated genomic DNA were cleaved from the surrounding chromosome, an isolated gene was, in fact, a new chemical entity. Similarly, several justices suggested that because cDNA was not found in nature, it too, was patentable – even if it was simply the product of reverse transcribing an mRNA sequence. (For a further breakdown on the oral arguments themselves, see Stanford’s Center for Law and the Biosciences’ oral argument recap.)

But it seems that at least five justices – and thus, a majority – believe that patents on isolated DNA are not eligible for patent protection. They don’t seem to buy the argument that simple covalent cleavage renders something a new chemical entity. The Court and lawyers deployed various analogies to make this point: gold from ore, a piece of wood from a tree, a liver from a patient, etc. It seems less clear, however, whether a majority will similarly rule cDNA to be patent ineligible.

Continue Reading »

Media, NIH, Research, Science Policy

NIH deputy director discusses blogging and science policy

NIH deputy director discusses blogging and science policy

Rock Talk, a National Institutes of Health (NIH) blog on extramural research policy, debuted two years ago as a way to enhance transparency about how the federal agency develops policies and present data that influence such decisions.

In a commentary published yesterday in Nature, Sally Rockey, PhD, deputy director for extramural research at the NIH, discusses her motivation for launching the blog and how it has increased dialogue with constituents about science policy. She writes:

We learned a lot about our constituents’ interests and needs through the blog, and we have been able to highlight behind-the-scenes data, actively engage the community in policy-making and provide insight into our decisions. Without public input, effective and impactful policy cannot be created. My blogging experience has convinced me that using social-media platforms is one effective way for science-funding agencies to successfully support research.

The blog is not the official vehicle for communicating policy changes. We have the NIH Guide for Grants and Contracts for that. And we have official channels for soliciting public feedback — through requests for information in the NIH Guide, for example. But the blog allows me to extend that conversation to people worldwide, many of whom I would not be able to reach in other ways. People are sometimes concerned that offering a dissenting opinion to NIH officials might affect their chances of getting funding. Although that is absolutely not the case, one advantage the blog does have over some other channels is that it allows people to remain anonymous if they wish.

In addition to fostering conversations on policy, Rockey offers examples of how the blog has allowed her team to provide real-time updates during national emergencies, such as Hurricane Sandy, and debunk urban myths about NIH-supported research.

Previously: Veteran blogger offers tips for starting a science blog

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