Source: http://www.kanebiolaw.com/2012/11/
Timestamp: 2019-04-21 15:05:03+00:00

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Today, the Supreme Court granted the petition for certiorari in the gene patent litigation, Association for Molecular Pathology (AMP) v. Myriad Genetics et al. The case focuses on the Myriad Genetics patents on the BRCA1 and BRCA2 (breast cancer) genes. This grant of review follows several years of the patentable subject matter challenge from a coalition of plaintiffs that has made its way through the lower courts, ending this summer with the Federal Circuit upholding the gene patents (again, following the Supreme Court remand to reconsider in view of Mayo v. Prometheus). Three questions were presented in the petition to the court: the patent eligibility of the genes, the eligibility of some method claims, and the last question involving the clarification of standing in the case. The Court will only consider the first question: Are human genes patentable? The Court must consider how to define an an isolated gene (isolated DNA) – as either a product/law of nature (not patentable) or a nonnaturally occurring processed product (patentable). Earlier this year, the Court issued its opinion in Mayo, invalidating a patent claim to a method of optimizing drug dosage which had the effect of preempting a law of nature (a natural correlation). At stake in AMP is how to define the product of nature doctrine in modern biotechnology - whether genes are to be defined by structure (the chemistry argument) or function (the genetic argument). The Federal Circuit took the chemistry route this past summer in its AMP decision, finding enough chemical alteration of an isolated gene to confer patent eligibility. In an amicus brief I filed this summer, I argued that the genetic fidelity (natural DNA sequence) of the isolated genes means that such patenting preempts the genetic code (law of nature), and, in addition, the genetic fidelity further characterizes the molecule as an unpatentable product of nature. From either analytic route, I conclude that genes are not patentable: the genes have a specific patent ineligibility because such patenting preempts a law of nature, and they have a general patent ineligibility because they are products of nature. The first theory (preempting a law of nature) resonates with Mayo; the latter theory (product of nature) resonates with Funk Bros. v. Kalo (1948). Genetic fidelity is not trivial; it is essential to the use of an isolated gene as a testing reagent.
What will the Supreme Court decide? The Supreme Court has exhibited a sensibility which accords significant weight to its role in protecting a public domain in science (the Court has established and refined a set of judicially-created exclusions - laws of nature, natural phenomena, abstract ideas - from patentable subject matter over the years, despite statutory silence). In Mayo, the Court stated that "even though rewarding with patents those who discover new laws of nature and the like might well encourage their discovery, those laws and principles, considered generally, are ‘the basic tools of scientific and technological work’” (quoting Gottschalk v. Benson (1972). The Court did not hesitate to strike a blow against business method patents in Bilski v. Kappos (2010), despite more than a decade of such patenting. With reference to Mayo - and to Justice Breyer's public domain-centered dissent in Labcorp v. Metabolite (2006) - there is a fair chance that the Court could side with the 2010 district court opinion, which found that the "claimed isolated DNA is not markedly different from native DNA as it exists in nature," and, as a result, the gene patent claims were invalid. AMP v. Myriad is not only important for the further clarification of the patent eligibility doctrine, but it has implications for the genetic testing industry (business models that depend on patenting isolated biological molecules) and for women's health (possible future development of a robust marketplace and an unfettered research climate for genetic testing involving the critical BRCA1 and BRCA2 genes). The case has also been a model for assembling a complex coalition of plaintiffs (researchers, genetic counselors, women patients, cancer survivors, breast cancer and women's health groups, and scientific associations) whose diverse interests illustrate the real-world consequences of what may appear to be solely theoretical patent law doctrines.
The limits of what can be patented in the life sciences continue to be refined by this period of active litigation in which foundational questions over patentable subject matter - 35 U.S.C. 101 - are receiving judicial attention. The Federal Circuit has just expanded on its jurisprudence for the patent eligibility of diagnostic testing methods which utilize either biochemical or genetic markers to determine the clinical status of an individual. In Perkin-Elmer, Inc. v. Intema Limited, the court invalidated patent method claims which relied on a series of prenatal measurements of known biological markers, performed through blood testing or ultrasound, to determine whether a woman has an elevated risk of carrying a fetus with Down’s syndrome. In Mayo v. Prometheus, decided earlier this year, the Supreme Court invalidated a patent claim to a method of optimizing drug dosing because the claim did no more than capture a natural biological correlation. Patent law doctrine does not allow the patenting of laws of nature, natural phenomena or abstract ideas. Yet, deciding whether a patent claim adds inventive weight to natural subject matter is not a simple test. The courts have often focused on whether a patent claim would actually "preempt" the use of a natural biological fact or phenomena if it were to issue. Would the patent holder effectively capture uninvented scientific information? This question has also been considered in the gene patent case, Association for Molecular Pathology (AMP) v. PTO, where the Federal Circuit invalidated method claims which did no more than use the fact that certain DNA mutations are correlated with elevated breast cancer risk. In Perkin-Elmer, referencing AMP, the court said that "the stricken claims there are indistinguishable from those before us." Further, the court stated that " Intema also claims a law of nature: the relationship between screening marker levels and the risk of fetal Down’s syndrome." With reference to the invalidated claims in AMP, the Perkin-Elmer court stated that "the stricken claims there are indistinguishable from those before us."The lineage of this decision is clear: “The Supreme Court’s decision in Mayo and this court’s recent decision in [AMP] dictate the result we reach today.” This case thus builds on the Mayo and Myriad framework for the analysis of method claims in the life sciences that are anchored in the recitation of a law of nature or natural correlation. In a reference to the possibility that the patent claims impermissibly preempt, the court stated that "anyone who wants to use this mental step or natural law must follow the claimed process." Thus, valid method claims in the diagnostic arts require more customized treatments of natural subject matter in order to qualify as an “inventive concept” and to avoid preemption over basic scientific subject matter. Further to the march of patentable subject matter cases through the courts, we await the Supreme Court's decision on the plaintiffs' petition for certiorari filed in AMP v. USPTO; the petition is scheduled for the Court’s conference tomorrow.
During most of 2012, a voluntary moratorium on high-risk H5N1 influenza virus experiments has been in place, following a controversy last winter. At that time, it was revealed that two laboratories had succeeded in creating apparently pandemic-capable H5N1 influenza strains, and were on the verge of publishing their research. The post-9/11 climate in the U.S. had seen the establishment of the National Science Advisory Board for Biosecurity (NSABB) to oversee and advise NIH on dual-use research (potential information, techniques and materials that can be used for benign or malicious purposes). A 2004 National Research Council (NRC) report had called for a more exacting institutional review of grant proposals for “experiments of concern” – that would have included these projects, as they are called "gain of function" experiments - the research produces a more, not less, dangerous virus. Last year, as concern grew over the announcement that new pandemic-level viruses had been produced in a laboratory, an immediate sense of crisis ensued, with the NSABB recruited to advise the journals regarding the suitability of publication. The debate focused on whether publication details should be released or curtailed (details included which DNA mutations made the influenza virus more deadly). There was no official attempt to shut down publication; however, the NSABB initially recommended that the scientific journals decline publication. It later reversed course and endorsed the publication of one in full (here), and one redacted (here).
Further, an international effort by influenza researchers led to agreement on a voluntary moratorium on gain-of-function experiments with H5N1. Their statement declared a “voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals.” This moratorium continues to be in place (and it echoes the 1975 Asilomar conference declaration of a voluntary moratorium on some recombinant DNA research). In July, Dr. Anthony Fauci (director of NIAID, which funded the initial research) had argued for a continued pause. A more recent debate over the continuing need for such a pause occurred in the journal mBio (American Society for Microbiology, ASM). Proponents of restarting such work argue that pandemic preparedness requires anticipating how the influenza virus can adapt and become more dangerous; others caution more delay and cite a combination of biosafety and dual-use research concerns. What’s clear is that these issues are not new and are not resolved; they were certainly anticipated by 2001 as the anthrax attacks raised the stakes for domestic terrorist incidents involving pathogens. As suggested by the 2004 NRC Report, NIH needs to frontload a dual-use review process at the level of funding decisions; such a review could authorize funding if the biosecurity measures are satisfactory but proactively manage a publication strategy, depending on results. Further, the mandatory physical security for such research (containment) needs to be standardized (it is not) before such work is funded. We might be on the verge of more official response to these unresolved questions. At the upcoming NSABB meeting next week, the committee will be discussing dual use research guidelines and NIH funding criteria for high-risk H5N1 influenza research.
The Supreme Court has agreed to hear the challenge to Maryland's DNA database expansion in a case that will test the constitutionality of DNA profiling practices in law enforcement which increasingly include those arrested for various crimes (federal and in 28 states). The case is King v. Maryland, handed down last September. As reported earlier here, when King was handed down, the Supreme Court (at least Justice Roberts) appeared to signal its disagreement with the Maryland court, to the point of granting the state’s request for a stay. The Maryland DNA Collection Act mandates DNA collection from those arrested for a “crime of violence, an attempted crime of violence, a burglary, or an attempted burglary.” The collection and profiling of those individuals leads to their inclusion in the state and federal (CODIS) DNA databases (current CODIS statistics show about 1.2 million arrestee profiles in the national database, and about 10 million profiles of convicted offenders). The Court will contend with the continuing project of defining the “reasonable expectation of privacy,” derived from Katz v. U.S. (1967), to weigh the constitutional challenge against asserted government interests in prevention and prosecution of crimes. Privacy interests are further attenuated (reduced) for those in the criminal justice system; to date, two federal appellate courts have considered the DNA profiling of arrestees and upheld the practice against 4th Amendment challenges. In 2011, in U.S. v. Mitchell, the 3rd Circuit upheld the federal DNA Fingerprint Act, enacted in 2006, which authorizes DNA collections from those arrested for federal crimes. Just this year, in Haskell v. Harris, the 9th Circuit upheld the California state law that authorized DNA collection from arrestees. However, Haskell has now been reheard by the 9th Circuit en banc (see here), and this case has taken a new turn with new research from the ENCODE consortium suggesting that DNA profiling may be more biologically informative than previously thought (is the DNA profile in CODIS no longer a neutral identifier, and thus less private, altering the Katz analysis?). Scientific consensus may be getting murkier, leading to more, not less, legal ambiguity.
Somewhat surprisingly, this will be the first case on DNA databases that the Supreme Court has taken, having denied certiorari for the earlier phase of 4th Amendment challenges to DNA collection, which focused on the claims of those actually convicted of crimes (e.g., U.S. v. Kincade, 9th Cir. 2004). The federal courts are generally in consensus in rejecting 4th Amendment challenges from those whose DNA profile is included in a government database because of an actual conviction. This case becomes the Court's second look in a year at the 4th Amendment in the context of developing technologies. In U.S. v. Jones, issued in January, the Court ruled that the warrantless use of GPS tracking on a motor vehicle violated the 4th Amendment, employing the anti-trespass norms embedded in the 4th Amendment to find an unreasonable government intrusion into a protected personal zone. Both Jones and King (when decided) will now provide further elaboration of how 4th Amendment protections coexist with rapidly changing technological capabilities; these are the type of cases that have been long-awaited since the 2001 U.S. v. Kyllo, where the Court ruled that warrantless thermal imaging of a home violated the 4th Amendment.
The election results are in, with consequences for several high-profile biotechnology issues at stake. Voters rejected California's Proposition 37, which would have required the labeling of genetically engineered (GE) foods in the state (see here). A vigorous campaign occurred in the state, of which opponents outspent supporters by about 5 to 1. An effective source of opposition to the measure was based on arguments that this new law would have adverse economic consequences - for consumers (higher prices), businesses (compliance) and a cash-strapped state (administrative costs). The final vote was 53% opposed, 46% in favor; this would have been the first state to enact such a law. The movement to label GE foods continues, with upcoming efforts on deck in Washington and Oregon. In a separate issue, the reelection of President Obama cements his policy of allowing federal funds to be used for embryonic stem cell research (see here), so this biotechnology sector has stability for at least several years. At a meta-level, impacting the major life science agencies such as NIH and the FDA, neither house of Congress changed hands (keeping committee leaderships in place), so that leadership of key committees in the House, such as the Committee on Science, Space and Technology, remains a GOP preserve, while the Democrats retain control of the Senate and its Committee on Health, Education, Labor and Pensions (HELP). The Obama reelection also locks in the Affordable Care Act (see here). Lastly, Charles Darwin received 4,00 write-in votes in a Georgia congressional election where the incumbent Rep. Paul Broun (R), a member of the House Committee on Science, Space and Technology, is an outspoken opponent of the theories of evolution, embryology, and Big Bang cosmology. Broun was reelected.
Can the federal government expand the use of a patented invention that was developed using federal research grants? The Bayh-Dole Act of 1980 sought to accelerate the transfer of federally funded research into practice, real world use; toward that end, the law allows federal grantees (such as a university) to pursue patent rights for the fruits of the federally funded work. A little-known provision in the Bayh-Dole Act gave authority to any federal agency that funds research, such as the National Institutes of Health (NIH), to order a “march-in” of patent rights where the funding agency determines such action is necessary to achieve the goals of the statute. This authority is held by any federal granting agency/department (e.g., NASA, DOE, DOD). Effectively, then, NIH can compel a patent owner to allow third parties to make and use the patented invention. The patent owner would be reasonably compensated for the use. March-in authority is justified when "action is necessary to alleviate health or safety needs which are not reasonably satisfied by the contractor, assignee, or their licensees" or "action is necessary to meet requirements for public use." The march-in provision of the law has never been used by NIH, despite several formal requests over the years, citing the unaffordability of an AIDS drug, unavailability of a federally-funded stem cell technology, or drug (Fabrazyme) inaccessibility due to manufacturing shortages. In all of these instances, NIH has conducted a review of the request, but declined to exercise its authority. A 2009 GAO study found that most federal granting agencies considered the march-in authority to be useful, but expressed concerns about a "chilling effect" on commercialization and technology transfer from any actual exercise of the right.
A new march-in petition to NIH has been filed by a coalition, including Knowledge Ecology International (KEI) and Public Interest Research Group (PIRG), asking the NIH to exercise march-in authority to increase access to the widely used Abbott AIDS drug, ritonavir (Norvir) (citing comparative per pill prices of $12.63/U.S. vs. e.g., $1.54/Italy, $1.46/France). This latest petition echoes a march-in request made to NIH in 2004, where a sudden increase in the price of Norvir immediately threatened access for AIDS patients. In its response to that petition, stating that “NIH believes that the issue of drug pricing is one that would be more appropriately addressed by Congress,” the agency denied the request. Here, the petition argues the necessity for a march-in for a number of reasons, primary focusing on an excessive price in the U.S. relative to similarly economically situated countries, but it further invokes an ADA-related argument on behalf of AIDS patients and cites adverse consequences for U.S. businesses seeking to be globally competitive. The current petition attempts to provide a metric for ascertaining when a cost would not be “reasonable” – suggesting a comparative study of U.S. prices vs. those in other income-equivalent countries. In addition to the specific relief requested, the petition asks NIH to formulate a policy that would include conditions warranting a use of the march-in mechanism, specifically where the U.S. price is higher than that charged in countries with similar income levels, and where the patent rights are frustrating the use of a dependent technology, e.g., a combination drug product. There is no reason to believe that NIH will be more receptive to this march-in request than to any of the previous filings, but the petition does attempt to quantify when the activities of a patent owner who controls a patented invention derived from federally funded research do not result in a “reasonable” satisfaction of health needs. As the agency did in 2004, NIH is likely to suggest that Congress is the appropriate venue to address any drug price standardization (federally funded research or not) and that the Federal Trade Commission is the appropriate venue for focusing on anticompetitive behavior. Notwithstanding the confounding variable of dissimilar national health care systems, this effort does prod the NIH to provide some definition for what reasonable implementation of a patented invention entails; to date, there has been no development of a march-in standard from NIH, and this dormant statutory authority has little definition.

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