In contrast to so many current political debates–climate change, abortion, health care–intellectual property law often appears to occupy a rarefied perch accessible only to patent experts, clerks and judges.  Patent policy is unnervingly complicated, with deceptively simple patent laws that are burdened with complicated webs of judicial interpretations.  It is little wonder, then, that most of us take for granted our government’s policy of granting and enforcing patents–if only as a cognitive coping strategy.  This complexity-induced apathy, by the way, suits patent lawyers just fine, and might be acceptable most of the time because, as in the case of an undersea oil-well blowout-preventer, patents may work pretty well, except when they don’t.

Patents on human DNA sequences (at least 20% of our genes are locked up) are increasingly viewed as deterrents to a new generation of genetic-diagnostic technologies, as well as to basic biomedical research itself.  That is the belief held growing number of physicians, researchers and legal experts, as well as this author.

Why do I use the word, “belief”?  Simply put, though the specifics of patent law are largely excluded from raucous public debate, the costs and benefits of patent reform are nevertheless as hypothetical, and worthy of argument, as in the cases of health-care reform, climate-change strategy or nuclear disarmament.  Proponents of the current system claim that the current patent regime is nothing less than vital to innovation.  As in any debate, those in favor of the status quo can point to experience, arguing that current technology would not have arisen without patent protection.  The apparent conservatism of this position belies the fact that our current patent regime–and any patent regime–is an artificial, legislated concept.  Defending it from alteration by claiming that it is an optimal policy is, thus, rationally unfeasible.

Some of the current momentum behind the reform of gene patent policy results from evidence that future genetic tests will be hamstrung by patents held by universities and companies–patents that give these organizations control over virtually any use of the human genes they claim.  That is the conclusion shared by a recent report from the HHS Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS).  The prediction that patents will impede progress may not, in itself, be sufficient reason to make changes to the policy.  However, the Committee points out the exceptionalism of patient care:

Indeed, in the realm of commodities or consumer electronics it may well be that dramatic harms and a profound lack of benefit should be required to compel any recommendation for change. But genetic tests affect patients’ lives and health.  Thus, the current system’s net negative effects on test development and patient access to these tests argue strongly for the narrowly tailored changes that are proposed.

These proposed changes are two-fold: (1) a diagnostic test exemption, allowing human genes to be analyzed even if they are protected from other uses (i.e. as therapeutics) by patents; and (2) a research exemption, allowing any use of patented genes in the pursuit of biomedical research.  This second exemption may come as a surprise to many, even to scientific researchers themselves.  Many scientists I’ve talked to either assume that common law (or common sense) already exempts their work from violating patents (mostly because it is unbelievable to many genetic researchers that DNA sequences could be patented in this way).  However, court decisions have decreased the research exemption to nil.  The SACGHS report argues for the clear enunciation of the legality of research on patented genes, if only to promote the rule of law.

Agree or disagree with these proposals–that is their major benefit!  They give something concrete to agree or disagree with to those citizens (especially relatively apolitical research scientists) who may have felt sidelined by the complexities of patent law debates.  Furthermore, gene patents are a natural starting point for a more general debate over patent policy because they affect anyone who intends to ever get medical care.

I’m back from defending my thesis (apparently successfully), just in time for  big news in the biomedical patent world.  The summary judgment ruling against Myriad Genetics and its BRCA gene patents, announced yesterday, brings up many questions about the future of patents covering genes and, potentially, other biological phenomena.   Obvious, however, is that the US patent office (USPTO) was shamefully uncritical of the claims from the original patent applications, a problem that extends to many, many similar patents.

Valid patent claims are meant to be narrow and novel but, by claiming invention of a short (15 nucleotide) DNA sequence, the BRCA1 patent clearly violates these criteria.  This is the conclusion that Duke researchers elaborate in a recent investigation, where they elegantly demonstrate what should be obvious to anyone with a minimal understanding of statistics (which was clearly not the case for the patent examiner).  The BRCA1 patent claims (in language similar to many gene patents): “An isolated DNA having at least 15 nucleotides of the DNA of claim 1″ (claim 1 being the protein sequence BRCA1).  Thomas B. Kepler, Colin Crossman, and Robert Cook-Deegan at Duke calculated that BRCA1 contains 5,575 individual 15-nucleotide sequences (15-mers).  Since the same protein sequences can be encoded in different DNA sequences, there are actually 1.6 × 10⁶ 15-mers that could encode the patented sequence of BRCA1.  As there are only 1.07 × 10⁹ possible 15-mers (DNA only has four letters), the patent could actually cover 1 in 600 of all possible 15-nucleotide DNA sequences (1.6 × 10e6/1.07 × 10e9).  The authors calculate that an average human gene would have 15 of the 15-mers covered by the patent! It should be noted (and this is a compliment, not a criticism) that this theoretical analysis requires nothing more than a calculator.  Searching for DNA or protein sequences can be done, for free, by anyone with a web browser; it was a bit more difficult, but not impossible, when the Myriad patents were filed in the late ’90s.  The merit of patenting such sequences may be debated as a point of policy; their novelty and uniqueness may not.

The court didn’t look into such specifics, but rather at the broader applicability of patent law to genetic information   Yesterday’s ruling focuses on whether the BRCA patents fall within the realm of “products of nature”, which have been held to be non-patentable.  The court found the genes to, indeed, be such a natural product.

Though there will certainly be much to debate in the ruling (which, no doubt, will be appealed), one of my favorite parts is a not-so-subtle rebuke of the USPTO, as well as Myriad’s argument that the government’s wisdom in granting patents should be respected:

The Federal Circuit has previously held that it owes no deference to USPTO legal determinations.  See, e.g., Arnold Pship v. Dudas, 362 F.3d 1338, 1340 (Fed. Cir. 2004) (“This court reviews statutory  interpretation, the central issue in this case, without deference.”).  While Congress has created a presumption of validity for issued patents, approximately 40% of patents challenged in the courts have been found invalid, demonstrating that this presumption is far from absolute.

yalepatents.org is on temporary hiatus while I finish my dissertation, but I thought I’d share some relevant sources of procrastination from the past few weeks.  First of all, On Point, the news program from WBUR-Boston, hosted a discussion on gene patenting and the Myriad/BRCA case.  Tom Ashbrook and his guests hold an accessible discussion, providing a nice starting point for those interested in gene patenting and biotech industry.  Notably, Chris Hansen of the ACLU defends his organization’s side in the case, arguing that a ruling in favor of the plaintiffs will not hinder biotech patents, but will promote competition and innovation in the industry.

Getting away from the economic immediacy of biotech intellectual property, some recent literature begs the question: what is professional bioethics good for?  Some of the recent discussion has been prompted by a new book, Observing Bioethics, by Renee C. Fox and Judith P. Swazey.  Though I look forward to reading it as soon as possible, Sally Satel provides a provocative review in The New Republic. Satel, a resident scholar at the conservative American Enterprise Institute, has written that the political and professional wing of the bioethics movement (in government and on hospital staffs) has distracted attention from its academic soul, transforming a philosophical field into an activist one.

Arriving as populist movements battle healthcare reform, this critique of bioethics is quite timely.  However, the anti-bioethics position conveniently, and attractively, avoids anti-elitism.  Satel argues in a recent essay from the Hoover Institution that bioethicists simply don’t have an expert advantage over average citizens the way geologists do in the climate change debate.  Rather, when they participate in the political discussion or on hospital review boards, “their value is mainly cosmetic or bureaucratic”.

Book Review: Who Owns You? The Corporate Gold Rush to Patent Your Genes, by David Koepsell.

Common wisdom holds that, at this historical moment of economic upheaval, war, and the broad threats to the relative homeostasis of our natural world (including from climate change and modern pandemics), the deliberation of law and policy occurs under a firm utilitarian mandate to maximize welfare with the inexact tools of government.  As political instruments, patents and copyrights are the utmost in means-to-an-end: “a highly pragmatic invention”, David Koepsell calls intellectual property rights, not entirely as a compliment.  In his newest book, however, Koepsell argues for a holistic reexamination of an increasingly far-reaching policy—the issuing of human gene patents.  His analysis is not limited to economic arguments for or against our current intellectual property regime.  Rather, he interjects with a question that many brush-off in the heated debate about scientific intellectual property: “is the current treatment of DNA as intellectual property consistent with its nature?”

The artificial, pragmatic nature of patent law makes it a fruitful policy realm to debate,  and the economic importance of patents make the system an attractive one to optimize.   This is a point made by many who argue that our current system of intellectual property protections is broken.  Koepsell goes a step further, however, in his philosophical analysis of gene patents and their relationship to justice.  Patents, because they have no status in natural law, must be judged solely by their economic effectiveness.   That does not mean, however, that patent protections are disconnected from a more fundamental notion of justice.  Gene patents, Koepsell argues from several philosophical and legal perspectives, actually “tend toward injustice”.

Koepsell provides historical context for intellectual property laws, and his treatment of gene patents is a useful primer on the subject.   He firmly argues that, pragmatic considerations or no, DNA sequences are not patentable because they are not intellectual property.  Even individuals who disagree with his philosophy cannot deny, as Koepsell demonstrates, that patents on human DNA sequences are a haphazard policy created without real political discussion.  In reality, they have were born largely of rulings by the judiciary, without legislative debate.  Because of the novelty of biological technologies, the judicial branch and society-at-large have been side-swiped by the collision of intellectual property and basic biology, and Koepsell writes that the results of this unpreparedness are increasingly shocking.  The ability of universities and companies to patent genes is a reflection of the blunt fact that “under most legal systems you do not own your body as authoritatively or completely as you own, for instance, a tennis racket or car.”

I predict that the accessible philosophical theory in Who Owns You will resonate with biologists, in spite of the utterly pragmatic operation of modern biomedical science—focused (as it should be) on delivering products and, even in the academy, profits.   True, biologists might not need an education in the ontology of DNA but, if they wish to have a place in the debate over intellectual property, they desperately need to be reminded that though the laws they investigate may be universal, the laws that govern our society are artificial and, by definition, suboptimal.

Indeed, as is painfully obvious in the evolution of biological patent jurisprudence, policy is often outpaced by science. Though a useful point of discussion, the fundamental significance that Koepsell gives to “genes” already seems a bit outdated. Technology developed since the genome and HapMap projects is delivering a much more complicated picture of how the molecules that make up our cells and bodies go about their business—providing a much larger potential pool of patentable material than was known even a few years ago.  If patenting DNA sequences is ontologically perverted, what about patents that cover other molecules and fundamental biological processes? This year’s Nobel Prize in chemistry, revealing the structure of the ribosome is, for all intents and purposes, locked up in patents.  Patents covering signaling molecules relevant to disease are no less a part of ourselves than DNA. And yet, as patentable objects, they blur the lines between universal biological entities and the artificial pharmaceutical designs that Koepsell and others accept as legitimate intellectual property.

The debate over patenting biological discoveries is so fascinating because it lies at the very intersection of controversial and emotional discussions such as economic growth and public health policy, social justice and privacy. It is all too easy to characterize the disagreement over intellectual property law (especially patents) as and elite feud among wealthy corporations, tech-savvy researchers and legal policy wonks.   Koepsell makes an extensive argument that gene patents should be recognized as a social justice and human liberty issue, yet still this leads to uncomfortable assertions. He qualifies his carefully argued grievances about bio-patenting by stating that, as an issue, it is “not comparable in scale to debates over civil rights leading to the abolition of slavery, or the civil rights laws of the 1960′s”. Such a “non”-comparison is no such thing; by staking moral ground somewhere below the largest dilemmas our society has confronted, Koepsell leaves the reader wondering how they should order gene patenting among their moral outrages.  Channeling ethical concerns over gene patenting is work of a more political sort, but Who Owns You provides a real philosophical foundation to anyone interested in the debate—including scientists who often consider (wrongly, I argue) the realm of legal and political philosophy outside of their purview.

Book: Who Owns You? The Corporate Gold Rush to Patent Your Genes, by David Koepsell.  Wiley-Blackwell, 2009.

Among other things, the healthcare debate has revealed to a large audience that our attempts at shaping the drug market are a cats-cradle of contradictory regulation.  A short history: Academic scientists who research future drugs are well aware of the Bayh-Dole Act which, in 1980, enabled researchers to patent and profit from taxpayer-funded innovation.  It was a bold attempt to encourage the movement of ideas from universities into the marketplace, where they can benefit society.   Meanwhile, the same federal government, cognizant that patents are actually monopolies designed to boost drug prices, realized that this effect must be mitigated to keep healthcare costs down.  In 1984, the Hatch-Waxman Act enacted regulations to encourage generic-drug manufacturers (representing the competitive threat that patents were meant to address in the first place) to contest the original patents in court.  How would the government get generic manufacturers to challenge the brand-name patents?  By promising the generic manufacturer a second round of protection from competition in the event it wins the dispute.  Today the Federal Trade Commission releases its new report, complaining that brand-name and generic drug manufacturers have found a profitable loophole by entering into agreements to avoid fighting over patents in the first place.  The proposed remedy?  The FTC wants to enact new legislation, making these anticompetitive agreements (over patent monopolies) illegal.

In their book, Patent Failure, James Bessen and Michael J. Meurer provide a sober critique of the U.S. patent system, focusing on doctrinal and technological shifts that have fundamentally disrupted the efficiency of the rights we bestow on technological inventions.  Their conclusion: during the last decade, our patent system has broken down because it failed to operate as a transparent system of property rights for inventions.  As a result of, among other factors, the huge cost of identifying relevant, competing patents–often claiming broad, early-stage innovations–the authors argue that patents cost industry more than they deliver, especially in high-tech sectors.

Bessen, a former software executive and currently lecturing at Boston University and Meurer, a law professor at BU, base their evaluation of the modern patent system on cost-benefit estimates for inventors of different scales in different industries.  Their conclusion, that patents do not provide the clear boundaries that are necessary in a workable system of property rights, is based heavily on a comparison of different industries.  Their research indicates that one modern industry where patents are particularly efficient–in that they impose very little cost on the profits they provide–is the chemical industry, where there is very little to argue about when it comes to a specific molecule that is patented.

Though they focus on software patents as an example the deleterious effects of overly vague patent claims, they highlight biotechnology as an industry similarly fraught with bad patent practices.  They blame the legacy of the Bayh-Dole act, encouraging universities to patent basic research, as well as a reduced requirement that patents be shown to have “utility”, a legacy of sometimes-conflicting rulings by the Federal Circuit during the ’90s.  The reduced burden of demonstrating that an invention is useful, or that it has been developed beyond the discovery stage has at least two negative implications: (1) that patents on basic scientific discoveries have become overly vague and discouraging to future inventors and (2) an oft-cited “flood” of patents has overwhelmed both the patent office and the ability of inventors and firms to search for patents that might compete with their ideas or research.

From the perspective of biomedical patenting, Bessen and Meurer’s contrasting characterization of chemical-pharmaceutical patents from those in the  biotech/biologic drug industry highlights one broad confusion over drug patents.  Contrary to many claims, the apparent success of traditional chemical patents does not portend the same happy fate for patents on complex biological drugs, much less patents on gene sequences or discoveries about basic biological systems.  When patent apologists claim that patents are essential for the drug industry, their enthusiasm may be outdated.

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Book – Patent Failure: How Judges, Bureaucrats, and Lawyers Put Innovators At Risk, by James Bessen and Michael J. Meurer (Princeton, 2008).

Academic research institutions and drug companies alike have been criticized for the high prices of their patent-protected drugs–particularly when these high prices are maintained in poor countries, where patients can least afford them.  Yale was the site of a conference last week where it and five other universities signed on to a statement of principles governing technology licensing in developing countries.  While this document is primarily a statement of shared philosophy, does it provide a good model for improving access to medicine in the poor nations–and perhaps even here at home?

Many would agree that universities should automatically subscribe to the principle of removing barriers to medication in developing countries; few but the most cynical would expect academic institutions to desire profits over the advancement of global health.  Unfortunately, it is unclear whether universities have the legal or practical potential to ensure that fruits of their researchers are equitably available–mostly because universities are not in the business of actually making the drugs.

The new licensing principles are crafted to address that disconnect between academic (and mostly publicly funded) research and the patient end-user.  In the context of academic biomedical patents, licenses are the contracts that the university (which reserves the right to patent anything invented within its facilities) signs with companies that agree to develop and market the innovation.  These licenses can contain anything mutually agreeable to both parties, but the main thing at stake is money: the university wants to get as large a percentage as possible in royalties, while still providing sufficient incentive to the company taking the risk of developing the drug.  The right of universities to profit, financially, from publicly funded research was codified by Congress almost thirty years ago, and major research universities have offices dedicated to working out license agreements.  What several universities, including Yale, have now agreed to in principle, is to exercise their rights as patent holders, to ensure licenses are written in such a way that, at the very least, they won’t be barriers to distributing discounted drugs in poor countries.

From an extremely idealistic vantage, it is appealing to compare these activist, principled licenses to the copyright licenses that have enabled the open-source software revolution, where creators invoke their intellectual property rights to ensure their creations are openly available.  Such a philosophy lies behind Creative Commons licenses, covering the words you’re reading right now, as well as the GPL, which has enabled a software revolution.

Of course, the comparison is completely metaphorical.  The major problem is that a license can be as activist and idealistic as anyone wants it to be, reserving rights to free distribution across Africa, Asia, Detroit and the Mississippi Delta, but it will have no impact unless the terms are acceptable to a drug company.

Furthermore, like many high-tech products, drugs are often born of quite complicated intellectual-property parenthood.  A company might license a research patent from a university, but then make several more patentable innovations, perhaps related to the process of actually manufacturing the drug, before the medication enters the marketplace.   Those who negotiate licenses on behalf of universities will have to be exquisitely shrewd to anticipate such complexities, and ensure that they can retract licenses if drug companies don’t follow through with equitable drug distribution.

The proposal enshrining the new guiding principles recognizes the pitfalls in ensuring access to medicines.  Time will tell whether universities can, within the current patent regime, exert a measurable influence over drug distribution, or whether their new principles are merely P.R. posturing.

Finally, by stating the principle of equitable access should be embodied in license agreements, how long can universities ignore patients here at home, in the U.S., that can’t afford medicine?  Drug companies are afraid that cheap drugs distributed even across the ocean in Africa will make it back to rich countries, diluting their market share and profits.  However, poverty is as globalized as ever, global warming threatens to bring tropical diseases to the temperate homeland, and meaningful health-care reform remains elusive.  Is it possible for Yale and other institutions to remain true to their goal of “implementing technology transfer strategies that promote the availability of health-related technologies”, without doing the same at home as in poor countries?

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More reading:

• Universities Allied for Essential Medicines: detailed proposals for Equitable Access Licenses.
• Yale press release.

Robert C. Pozen writes in today’s New York Times of his proposals for refitting our patent system, with a particular eye towards the painful inability of patent examiners to judge applications in fields outside their expertise.   Pozen’s proposal is that other researchers or experts in the appropriate field be allowed to officially comment on applications, after they are made public.  This modest proposal is in line with the general expectation of scientists that their work will be scrutinized harshly but fairly and–most importantly–by their peers.

It’s a familiar story, told in elementary school science lessons.  In 1867, Alfred Nobel patented Dynamite–a ground-breaking technology if there ever was one–which exploded into uses in rock quarries, road projects and the on the battlefield.  The wealth yielded by the sale of dynamite allowed the famous Swede to finance the Prize, which today was awarded for the beautiful research that led to 3-D structural models of the ribosome.

It could be argued that the word “fundamental” could be applied to any number of molecular machines that are essential to the livelihood of practically every cell in our bodies.  But ribosomes are in the very middle of the dogmatic process of turning genes to proteins, and they are extremely well-conserved throughout evolution.  And, as I’ve written before, these revealing biological discoveries will be protected by patents for years.

The New York Times news update described ribosomes this way:

If the sequence of lettered nucleic acids in the DNA form the blueprint for life, ribosomes are the factory floor.

It was a kind of reverse-engineering of this “factory floor” that constitutes the Nobel-winning work.  The laureates first had to crystallize various parts of ribosomes, an extremely complicated task given the size and complexity of these molecular complexes.  These crystals were analyzed with a very sensitive X-ray device, yielding information that, when reconstructed by a computer, can be modeled into a three-dimensional diagram of the molecular structures.

Other than being extremely beautiful, these structures are vital for determining how ribosomes interact physically with other molecules.  These other molecules include ones that  ribosomes would normally commingle with in the cells, like RNA.  More usefully, perhaps, this information can be used to design small, artificial molecules–drugs–that could bind to a part of the ribosome to alter its function in some way, or perhaps to disrupt it completely.

Tetracycline, designed and manufactured by bacteria. (Wikimedia)

A particular bacteria, Streptomyces, has been doing this kind of “drug-design” work for a very, very long time.  Streptomyces evolved various small molecules that bind to ribosomes and disrupt their function. These natural, bacterial molecules–tetracycline, neomycin and others–are now found in pills and over-the counter ointments.  As antibiotics, they kill other cells by attaching to and rendering their ribosomes useless.

Using the Nobel-winning structures to design the types of molecules that these bacteria have long been producing is a practice now protected by a number of patents.  Some of these patents, held by Yale in the name of the prize-winner Thomas Steitz and others, cover not only the process for determining the structure of the molecules, but also the computation used to design new antibiotics.  The Yale patents are currently licensed to Rib-X pharmaceuticals, a Yale-spinoff biotech company based in the New Haven area.

As always, there is an argument that intellectual property must be fully patent-protected before major investments can be made towards developing commercial products.  The patent holders and licensees surely believe that these products will be life-saving, and profitable, and I hate to rain on the Nobel Prize parade.  But should research so fundamental to life, such as the ribosome structure, be locked up for commercial gain–like Dynamite?  Should a private institution, such as Yale, have the only say over how ribosomes may be developed into new biomedical technologies?

A New York Times article from last week caught the eye of commentators on the business and law of intellectual property. The article describes an up-and-coming business model, already filling-up on on venture capital, that aims to streamline the process of licensing patents by setting up commercially organized patent marketplaces.

These patent auctioneers aim to insert themselves as efficient (and lucrative) middlemen between inventors and manufacturers, allowing prices to be negotiated for patents within an environment of open and well-informed trading.

Patent auctions have their detractors. Michael Masnick at Techdirt invokes Thomas Jefferson in proclaiming the theoretical weaknesses and practical costs of such markets:

Markets are for property exchange and the more efficient allocation of property. Ideas are not property, and making a market for them and holding them back doesn’t accelerate the pace of innovation, it retards it. Greatly.

It’s still unclear whether patent marketplaces can solve, even by auction-style bidding, the complicated task of putting a monetary value on patents. Putting a value on an idea is difficult enough, but patents, unlike, say, copyrighted music, are especially risky because they vulnerable to being challenged in the courtroom on the basis of their novelty and non-obviousness.

If commercial patent marketplaces gained traction, it seems likely that they would have a huge appeal to universities, which invest large amounts of money in their “technology transfer” or “cooperative research” arms. These offices are responsible for identifying research at the university that may be both patentable and lucrative, so that the university can make investments in writing up and applying for patents with the hope of returns from future royalties. (Universities can seek patents for research performed with federal tax-dollars, an arrangement made possible under the momentous Bayh-Dole Act of 1980). Successful patent marketplaces could decrease the costs and risks to the university of licensing their innovations, perhaps allowing them to privatize some of the work of technology transfer.

Anything that actually speeds the route from innovation to technology sounds like a good thing. However, the risk of patent auctions, particularly when applied to basic, academic biomedical research, is that they could further erode the stated purpose of that research by adding another layer between inventor and manufacturer. Research is performed and licensed not to make universities rich, but to save and improve lives.

We already let universities, public and private, take control of inventions that were made possible with public money. We may not, however, be doing enough to ensure that the social utility of these inventions is maximized during the licensing process.