Federal Panel Now Recommends Publication of Influenza Research

Events have shifted quickly in the aftermath of the disclosure of NIH-funded research that resulted in the production of new possibly pandemic-capable influenza H5N1 viruses in two laboratories, at the University of Wisconsin (Yoshihiro Kawaoka) and in the Netherlands (Ron Fouchier). Because of the possible threat that these viruses could pose, immediate concerns were raised as to whether details of the virus structure and the methods for their construction should be available to the public. As a result, the normal publication process for the papers submitted by the two laboratories was shortcircuited by the December recommendation of a federal advisory committee, the National Science Advisory Board for Biosecurity (NSABB), that the research not be published.  This recommendation has been controversial and to some, alarming. Not all virologists have considered this necessary. For example, this recommendation was not supported recently during the convening of an expert conference by the World Health Organization; the participants recommended publication. Now, in the U.S., the NSABB has reversed course. At last week's meeting of the NSABB, the panel voted  to recommend full publication of the now-revised Kawaoka paper (in Nature), and for publication of selected excerpts version of the Fouchier paper (in Science). This removes the unprecendented scenario where both leading scientific journals halted their normal review and publication process upon the intervention of the NSABB, a committee established following 9/11 and the 2001 anthrax attacks to provide NIH with further expertise regarding the control of potential bioterrorist materials and agents and the facilities where they are handled. To date, this was the first instance where the committee extended its reach to consider if the release of scientific knowledge – in the form of peer-reviewed scientific articles - posed a significant threat.

Organic Farmers Appeal Dismissal of Challenge to Monsanto Patents

The proximity of genetically engineered (GE) crops to organic farming operations (non-GE) poses problems for possible contamination of the non-GE crops through the drift of pollen from the GE fields onto the non-GE plantings. Complicating this scenario is the possibility that contamination occurs through migration of patented GE materials, leading to potential claims of patent infringement. A closely watched lawsuit, Organic Seed Growers et al., v. Monsanto, was launched by a coalition of organic farmers seeking a preemptive ruling (declaratory judgment) of non-infringement and patent invalidity in contemplation of possible inadvertent contamination of their fields by Monsanto's patented transgenic seed materials (sometimes referred to as genetic trespass). Last month, a judge in the Southern District of New York ruled that no sufficient controversy existed to provide a basis for the plaintiffs’ lawsuit. As expected, the plaintiffs have now filed an appeal with the Federal Circuit seeking to reinstate their right to litigate the Monsanto patents in view of their apprehension of legal action from Monsanto. The standard for standing in declaratory judgment actions, applied in the context of a patent lawsuit, was set by the Supreme Court in Medimmune v. Genentech, where the Court pronounced a more flexible “all circumstances” that replaced the more rigid injury-nexus-relief test that had evolved from its earlier decision in Lujan v. Defenders of Wildlife. Yet, the Federal Circuit has recently applied this standard, in the context of AMP v. USPTO (challenging the Myriad Genetics gene patents): “this court has held that, to establish an injury in fact traceable to the patentee, a declaratory judgment plaintiff must allege both (1) an affirmative act by the patentee related to the enforcement of his patent rights,” and “(2) meaningful preparation to conduct potentially infringing activity.” In AMP v. USPTO, the Federal Circuit declared that only one plaintiff, Dr. Harry Ostrer, qualified for standing, in view of active assertion by Myriad’s active enforcement of its patent rights against Dr. Ostrer, and his stated intention to resume his genetic testing activities if the threat of patent infringement were lifted. In the farmers’ lawsuit, both of these elements for standing as emphasized by the Federal Circuit appear harder to prove: no direct legal actions by Monsanto against these plaintiffs (although the pattern of Monsanto patent enforcement has evidenced a willingness to convert contamination into patent infringement); and this absence of nexus then undermines the plaintiffs' assertion of preparation for activities that might constitute infringement (yet some plaintiffs are alleging refraining from farming due to their fear of litigation). Nonetheless, if the plaintiffs can successfully argue that the Supreme Court deliberately crafted a more flexible standard for standing in Medimmune – certainly recognizing a public interest in the adjudication of potentially invalid patents – that encompasses this novel factual pattern of perceived threat and potential assertion of rights, they may have a chance to revive the suit.

Supreme Court Sends Gene Patent Case Back to Federal Circuit

Today, and not surprisingly, the Supreme Court decided that it would not grant review of the pending patent law case on gene patents - Association for Molecular Pathology v. U.S. Patent and Trademark Office (AMP v. USPTO) - which had been sought by the plaintiffs’ coalition of patients, doctors and researchers. The Federal Circuit upheld the Myriad Genetics breast cancer gene patents in their July 2011 decision, generally rejecting arguments that genes are products of nature and cannot be patented. The Court announced that it would now send the case back to the Federal Circuit to reconsider in light of its Mayo v. Prometheus decision from last week. In the Mayo case, the Supreme Court ruled that the drug treatment method at issue could not be patented because the patent claim was essentially to a law of nature and effectively put a basic scientific fact under private control. Now, the Federal Circuit is to get another chance to look at gene patenting in view of the Supreme Court’s renewed emphasis in the Mayo case on the importance of avoiding patents on laws of nature or natural principles. I have argued in an amicus brief filed at the Federal Circuit that genes and genetic mutations cannot be patented as such patenting preempts the underlying natural laws of genetic science (the genetic code and genotype-phenotype correlations). The 2011 Federal Circuit decision (2-1) upheld the Myriad patents, partially relying on deference to the USPTO (which had been granting such patents) and further highlighting certain chemical alterations of an isolated gene to support patentability. The 9-0 Mayo decision from the Supreme Court addressed the eligibility of method claims in view of patent law's prohibition on patenting laws of nature, and its logic must now be applied to the composition patent claims on DNA. Conceptually, I think this can be done (here’s my central argument developed in detail) and the task necessarily focuses attention on the unique, template-oriented features of DNA, as distinct from other molecules. Can we imagine a DNA-centric decision that does not affect the patenting of other biomolecules? I think that’s possible. The unresolved gene patenting issue is the other prong of the patentable subject matter debate in biotechnology. It's not possible to avoid the fact that DNA/gene patenting (and its implications for the use of DNA in all kinds of genetic testing and applications) has specifically troubled many in the medical and genetic testing fields, because the paradigm of DNA patentability ramifies through the whole field of genetic medicine (and has caused real limitations for patients in some fields of genetic testing). Many of the same professional organizations (e.g., American Medical Association) that successfully opposed the drug treatment method in Mayo have also opposed the patents on the breast cancer genes, mutations, and genetic testing methods in AMP v. USPTO. It remains to be seen whether the Federal Circuit will now take a dimmer view of gene patenting in view of the Mayo decision; if it reaffirms its earlier endorsement of gene patenting, that conclusion could then be appealed back up to the Supreme Court. So we may have at least another year ahead before these current debates in biotechnology patenting are resolved. However, over 30 years have passed since Diamond v. Chakrabarty in 1980 (Supreme Court upheld a patent on a genetically engineered bacterium), with relatively little case law on these subjects in the interim. 

New York Becomes First State to Adopt All-Crimes DNA Database

New York State has broken new ground in the ongoing debates over the scope of DNA collection for state forensic databases: who must submit DNA? New York has now become the first state to implement an all-crimes DNA database, where anyone convicted of a crime, whether felony or misdemeanor, is now required to submit a DNA sample to the state database. Previously, the NYS database, established in 1996, only included those convicted of all felonies and some sex crime misdemeanors; the new legislation now targets all convicted individuals. The underlying theory supporting database expansion was articulated by co-sponsor State Senator Steve Saland: "The DNA databank expansion is particularly critical when studies show that persons who commit serious crimes have also often committed other crimes including lower-level misdemeanors." The legislation contains further provisions that expand post-conviction DNA testing for some criminal defendants. For nationwide legislative tracking, see here. Of concern is whether the expansion would contribute to any backlog in the processing of DNA evidence’ at least for now, the governor’s office does not believe that it will. The nationwide backlogs in the processing of DNA evidence are well-documented, particularly from the rape kits collected from rape victims; the federal government has intervened to clear out the backlog by providing funds for state laboratories. Since 2006, Congress has allocated $785 million to help state and local crime laboratories clear up unprocessed DNA samples and reduce existing backlogs. Without continued federal funding to assist local laboratories, many legislative expansions of DNA collection could lead to increased backlogs. Now that New York has instituted the all-crimes database, other states are likely to follow suit. In addition, legal debates continue regarding the expansion of DNA collection to arrestees (here is an earlier report regarding the expansion of DNA collection in New Jersey; here is a report on the recent 9th Circuit ruling that upheld the inclusion of arrestees in the California DNA database against a 4th Amendment constitutional challenge).

Mayo v. Prometheus: Supreme Court Says Drug Treatment Patent Violates Law of Nature Exclusion

Today, the Supreme Court has handed down a major opinion regarding patentable subject matter in biotechnology, the first such opinion since Diamond v. Chakrabarty in 1980.  Patentable subject matter asks whether a patent fits into the kinds of inventions that are eligible for patenting or whether it goes too far and extends into the impermissible categories of "abstract ideas, natural phenomena and laws of nature; " see here for background. Today's case is Prometheus v. Mayo; at issue was whether patent claims to a method of drug treatment which utilized a metabolic relationship to formulate drug dosage violated the long-standing prohibition against patenting laws of nature.  In other words, did the patent effectively allow its owners to monopolize the scientific fact that the administration of a drug caused certain metabolites to be produced in the body, and those levels could indicate potentially toxic drug levels? If a doctor simply used the relationship between drug metabolites and drug toxicity to determine dosage, would that become patent infringement?  If so, was this patent an undue extension of patent rights into the laws of nature?  These were the issues at stake here. The court, in a unanimous opinion authored by Justice Breyer (who had previously shown great interest in these questions in the 2006 LabCorp v. Metabolite case) stated that the patent claims added no serious inventive work to the underlying law of nature: “To put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well­ understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."

These patent claims illustrate a kind of patenting in biotechnology, where the use of a scientific relationship/law of nature forms the basis for a diagnostic or therapeutic treatment method patent claim. Where a patent does no more than simply dress up a law of nature for conversion into a patent method claim, it now stands vulnerable to invalidation under this line of reasoning from the Court. The Court referred to the possible anti-innovation effect of such patent claims, noting “the kind of risk that under­lies the law of nature exception, namely the risk that a patent on the law would significantly impede future innovation.”  In an accurate portrayal of how that can happen, the court noted “that very exclusivity can impede the flow of information that might permit, indeed spur, invention, by, for example, raising the price of using the patented ideas once created, requiring potential users to conduct costly and time-consuming searches of existing patents and pending patent applications, and requiring the negotiation of complex licensing arrangements.”  Finally, the Court reinforced the importance of the patentable subject matter doctrine in patent law, rejecting calls to subsume these difficult questions of line-drawing into other patent doctrines. So this case will have a tremendous impact on biotechnology patenting, cautioning against overly broad method claims that tie up the use of fundamental scientific observations. We are still waiting to hear whether the Supreme Court will take up the other outstanding issue in the patentable subject matter debates – gene/DNA patenting in AMP v. USPTO. The petition in that case has been filed; no decision yet. Over 30 years have passed since Chakrabarty was decided, in a case that made patent law receptive to the inventions produced from genetic engineering; currently, the patentable subject matter questions reflect decades of research into genes and genetic processes and how patent law can accommodate truly inventive efforts without putting basic scientific knowledge at risk of private control. Today, the Supreme Court struck a blow for the continuing validity of interrogating patent claims for adverse intrusion into the scientific public domain.

NIH and Dual-Use Research: Congress Focuses on H5N1 Virus

It was to be expected that the recent controversy over the deliberate genetic engineering of a possibly pandemic-level H5N1 influenza virus would not go unnoticed by Congress. Although much of the controversy regarding the research did center on whether the leading scientific journals would publish the details of the research (after being asked not to by the National Science Advisory Board for Biosecurity (NSABB), an NIH advisory committee) a threshold question remained: should the research have been done at all, or more precisely, funded by NIH?  The focus on publication was a concession to the reality that these viruses now exist, so attention focuses on containment, whether physical (obviously) or intellectual (publication strategy).  Currently, the journals are reviewing fairly detailed publications; the recent WHO meeting of public health and influenza experts expressed a preference for full, not redacted publication. But who is asking whether NIH should have funded this research?  Here it is: Congressman James Sensenbrenner, Vice-Chair of the House committee on Science Space, and Technology sent a letter to the White House Office of Science and Technology Policy (OSTP; the President’s in-house scientific experts) that asked the relevant question: “Is the NIH’s review system adequate to identify potentially dangerous dual use research?  Why did it fail to identify the avian flu research until it was completed and submitted for publication?” Note the attention in the letter to dual-use research (capable of benign and malicious uses) and whether NIH proactively considers this dimension when making funding decisions.  We might expect a Congressional hearing down the road, where both NIH (funding the research) and the NSABB (managing its publication risks) are called to account. However, full public discussion of the details of the work (to make this more complicated, the risk of the virus is now contested in a more recent and relaxed view of the dangers of the virus by investigator Ron Fouchier) might be resisted. Unresolved legal issues remain regarding the publication debate –  e.g., questions of First Amendment protection for scientific inquiry – but this is a grey area, with an advisory body (NSABB) issuing recommendations that lack the force of law. The larger question of research funding is even less clear, because NIH has wide discretion to establish the bases on which it allocates federal funding; nonetheless, Congress funds NIH annually and is legitimately positioned to magnify public scrutiny of research with potential biosecurity implications. We could imagine that a more rational scheme would consider potential complications of publication at the time of grant review and have contingencies on hand ex ante. The scramble to contain publication of the H5N1 virus details is testimony to a lack of regulatory foresight.

NIH Genetic Test Registry Is Online

The National Institutes of Health (NIH) has been in the process of designing a central repository for listing the genetic tests that are available in the U.S. This initiative created the Genetic Test Registry (GTR), which just launched last week. The site aims to be a centralized public database, but participation is voluntary and NIH rejected calls for mandating that genetic test providers list their services in the registry. The site was developed by NIH over several years, with the solicitation of public comments and public meetings. The functions of the site include “(1) encouraging providers of genetic tests to enhance transparency by publicly sharing information about the availability and utility of their tests; (2) providing an information resource for the public, including health care providers, patients, and researchers, to locate laboratories that offer particular tests; and (3) facilitating genetic and genomic data-sharing for re research and new scientific discoveries.” Prior to the creation of this registry, the NIH supported website Genetests operated a kind of clearinghouse for genetic testing; the new site now facilitates migration from Genetests to GTR; both sites include the very useful peer-reviewed GeneReviews resource. NIH features a prominent notice on the GTR site which reminds all who visit that the available information has not been verified by NIH and will not be; the notice is a subtle reminder of the absence of federal regulation for most genetic testing. Despite the voluntary nature of the new GTR registry, well-known network effects are likely to operate and create momentum for inclusion; a kind of federal imprimataur without regulatory oversight will certainly entice participation. Furthermore, as the public comes to regard the resource as at least an authoritative cataloging, failure to participate is likely to create a negative inference for any provider. Market forces will operate to make this registry an essential cost-free mechanism for genetic test providers to reach patients and health professionals.