September 2, 2013

New Gain of Function Experiments Proposed for H7N9 Influenza Virus

A declaration of intent to conduct “gain-of function” experiments on the novel avian influenza A(H7N9) virus has been published by scientists who wish to alter the genetic composition of the viruses to determine what genetic changes/mutations correlate with altered function. Gain of function (GOF) experiments on pathogens alter existing properties and can result in the creation of more dangerous pathogens; the goal is to gain insights into the relationship between genetics (structure) and function. The H7N9 virus emerged earlier this year in China, and to date the World Health Organization reports 135 human cases, with 44 fatalities. This new effort to study H7N9 is proposed by a consortium of scientists, including Ron Fouchier and Yoshihiro Kawaoka, who were the principal investigators for the experiments on HPAI H5N1 viruses that produced viruses with potentially increased human to human transmissibility. Those earlier experiments raised such an alarm that publication of the research was halted in the U.S. while the NSABB federal advisory committee evaluated the risk of publication (both were eventually published). The proposed experiments fall into the category of DURC (dual research of concern), defined as such: 
Dual use research of concern(DURC) is a subset of dual use research defined as life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security. 
The declaration of intent by the scientists is presumably an attempt to increase transparency and invite deliberation at the front end of the process and avoid the panicked reaction that followed the announcements of the earlier H5N1 experiments in 2011. The authors also include materials outlining the biosafety precautions that would accompany the experiments. Early official reaction from the CDC and NIH declares that such experiments will receive extra scrutiny before U.S. government funding will be made available, according to recently issued federal guidelines for DURC issued earlier this year. The CDC has also issued specific biosafety guidelines for working with the H7N9 virus. The following kinds of gain-of-function experiments were announced in the letter: 
•Immunogenicity. To develop more effective vaccines and determine whether genetic changes that confer altered virulence, host range or transmissibility also change antigenicity. 
•Adaptation. To assist with risk assessment of the pandemic potential of field strains and evaluate the potential of A(H7N9) viruses to become better adapted to mammals, including determining the ability of these viruses to reassort with other circulating influenza strains.
•Drug resistance. To assess the potential for drug resistance to emerge in circulating viruses, evaluate the genetic stability of mutations conferring drug resistance, and evaluate the efficacy of combination therapy with antiviral therapeutics. Also, to determine whether A(H7N9) viruses could become resistant to available antiviral drugs, and to identify potential resistance mutations that should be monitored during antiviral treatment.
•Transmission. To assess the pandemic potential of circulating strains and perform transmission studies to identify mutations and gene combinations that confer enhanced transmissibility in mammalian models (such as ferrets and guinea pigs).
•Pathogenicity. To aid risk assessment and identify mechanisms, including reassortment and changes to the haemagglutinin cleavage site, that would enable circulating A(H7N9) viruses to become more pathogenic. 
These proposed experiments – altering the critical variables of spread and virulence for the viruses, changing drug resistance and  vaccine susceptibility – will likely produce viruses that are potentially more dangerous than those we currently know about. The stated goal of such work is to learn which mutations alter the risk profile of a virus – confer pandemic potential – and use that knowledge to design vaccines or discover antivirals that can respond to these viruses. Further, it is argued that ongoing surveillance efforts can be focused on identifying virus isolates that display such mutations and pose an elevated public health risk, although this point is contested by other scientists. It’s not clear whether the NSABB will be involved at this early stage – to date, it has not advised on the merits of funding specific experiments which can be characterized as DURC. The recent tightening of federal review of such research will be put to the test with these proposed experiments as the investigators seek U.S. funds. With respect to the publication of results, the influenza researchers anticipate the possible fallout: 
To advance A(H7N9) virus research, findings should be shared in refereed publications. Investigators agree to adhere to guidelines for responsible communication of results and every effort will be made to put the results in context and reduce sensationalism. 
The questions that were raised by the H5N1 influenza controversy  - what criteria are to be used when evaluating the funding for DURC or what conditions need to attach to such funding – will now surface with this H7N9 research declaration – and their resolution might establish a template for future research proposals.

July 29, 2013

Post-AMP, Myriad Files Patent Infringement Suits Against BRCA1 and BRCA2 Testing Competitors

Several developments have followed last month's Supreme Court decision that invalidated Myriad Genetics patent claims to isolated genes; (AMP v. Myriad opinion). Within hours of the Court’s decision, several competitors announced plans to offer BRCA1 and BRCA2 genetic tests. Myriad has recently filed patent infringement suits against Ambry Genetics (California) and Gene by Gene (Texas), based on the assertion of patent claims from ten patents it holds to BRCA1 and BRCA2 related genetic materials and methods (including some with contested claims in the Supreme Court). The complaint against Ambry is here; the complaint against Gene by Gene complaint is here. The suits, filed in Utah federal court, could be an opening play to fully litigate these other patents or a maneuver to create licensing structures for these patented materials and methods. A strategy by Myriad to obtain a preliminary injunction against these companies would have to contend with the more rigorous scrutiny for such requests after eBay v. MercExchange (2006), where the Supreme Court reaffirmed the need to consider "public interest" in the award of injunctions, and the current climate might lend support for such an argument against any injunction. Ambry has indicated that it will “vigorously defend” its right to offer testing services.The Court’s invalidation of some of Myriad’s patent portfolio related to BRCA1/2 testing has clearly led to altered expectations regarding the state of the genetic testing marketplace. Evidence of this is the response from Senator Patrick Leahy, Chair of the Senate Judiciary Committee, to Myriad’s lawsuit, calling for the National Institutes of Health (NIH) to exercise “march-in” rights that it holds pursuant to the Bayh-Dole Act of 1980. That option applies to patents for which NIH provided federal funding (or other federal agencies). Apart from the march-in authority, the U.S. government retains a default mechanism, a compulsory license that allows it to use any patented invention (or authorize 3rd parties to do so) under the statutory authority of 28 U.S.C. 1498, which requires “reasonable and entire compensation for such use and manufacture.” Since the march-in authority has never been exercised by the NIH (see here), it is unlikely to respond to Leahy’s call. Nor is it likely that the government would regard the BRCA1/2 genetic testing controversies as critical enough to trigger the compulsory license mechanism. These disputes are likely to be settled more informally, and more quickly, as the high visibility of these tests will retain public attention and maintain pressure on Myriad to support the expansion of genetic testing options.

July 1, 2013

Connecticut and Maine Enact Genetically Engineered Food Labeling Laws But Delay Effect

Connecticut and Maine have become the first states to pass laws mandating the labeling of foods with genetically engineered (GE) ingredients (Maine law; Connecticut law). The laws, however, are conditional in that they will not take effect until a critical mass of similar laws is enacted by other states; thus, they remain pending in actual effect. The battles over the labeling of GE food have continued for years, with efforts at state and national levels (see here and here). Maine will mandate the phrase “Produced with Genetic Engineering" and the Maine law contains this synopsis: 
This bill requires disclosure of genetic engineering at the point of retail sale of food and seed stock and provides that food or seed stock for which the disclosure is not made is considered to be misbranded and subject to the sanctions for misbranding. The bill provides that food or seed stock may not be labeled as natural if it has been genetically engineered. The bill exempts products produced without knowledge that the products, or items used in their production, were genetically engineered; animal products derived from an animal that was not genetically engineered but was fed genetically engineered food; and products with only a minimum content produced by genetic engineering. The bill also provides that the disclosure requirements do not apply to restaurants, alcoholic beverages or medical food. 
The Maine law embeds the following trigger: it “goes into effect when five other states, or any state, or states with a total population of 20 million people, enact labeling requirements for genetically modified (GM) foods.” The Connecticut law dictates labeling “in the case of such food for retail sale contained in a package, with the clear and conspicuous words: "Produced with Genetic Engineering." Here is a similar trigger in Connecticut, activating the law in a year where the following conditions occur: 
(1) Four states, not including this state, enact a mandatory labeling law for genetically-engineered foods that is consistent with the provisions of this subsection, provided one such state borders Connecticut; and (2) the aggregate population of such states located in the northeast region of the United States that have enacted a mandatory labeling law for genetically-engineered foods that is consistent with this subsection exceed twenty million based on 2010 census figures. 
The northeast region defined in the Connecticut law consists of Maine, Vermont, New Hampshire, Massachusetts, Rhode Island, New York, New Jersey and Pennsylvania. It could be argued that the approach of Maine and Connecticut to a GE food labeling law – not with immediate effect, but conditional on other political developments – can recruit support from hesitant politicians because it remains aspirational. That might encourage other states to follow suit. At the federal level, the Genetically Engineered Food Right-to-Know Act, has been introduced to mandate a federal scheme for GE food labeling; such bills have been introduced for years in Congress. Prospects for federal legislation, however, remain dim.

June 18, 2013

Pay to Delay? Supreme Court Authorizes Distinct Antitrust Scutiny of Reverse Payments in Pharmaceutical Patent Litigation

The Supreme Court has issued its decision in Federal Trade Commission (FTC) v. Actavis, a case that presents the issue of pay for delay settlements between brand name and generic drug companies - a legal dispute at the intersection of patent, antitrust and food and drug law. Essentially, this case scrutinized a particular form of settlement practice in a patent infringement suit between a brand name drug patent holder and a generic competitor – facilitated by the intricate mechanics of the 1984 Hatch-Waxman Act, which rewired the drug approval process for generic drugs and accelerated the entry of generic drugs into the marketplace. When a generic company prepares for market entry, it may undertake actions which trigger an infringement lawsuit (most commonly in the statute's Paragraph IV certification in which the generic asserts that the brand name patent is either not infringed or is invalid) from the brand name company. In these suits, although a brand name company sues a generic competitor for patent infringement, the litigation flips and the plaintiff (brand name) might decide to pay the defendant (generic) to drop the suit and delay its entry into the market – hence, the "pay for delay" or “reverse payment” settlement. As a result, generic entry is delayed by the deal made with the brand name; in addition, potentially invalid patents are not challenged or litigated for validity. As Justice Breyer explained: 
The payment in effect amounts to a purchase by the patentee of the exclusive right to sell its product, a right it already claims but would lose if the patent litigation were to continue and the patent were held invalid or not infringed by the generic product.
These reverse payment settlements have been controversial – so much so that the FTC tracks these settlements, under Congressional mandate (40 reported in 2012). Are these settlements anticompetitive, potentially violating the antitrust laws? The FTC thought so and challenged one of these in FTC v. Actavis (as violating Section 5a of the Federal Trade Commission Act), which made its way to the 11th Circuit – there, the appellate court said that the FTC could not challenge the settlement on antitrust grounds, because the patent holder was not exceeding the effective rights granted by the patent – that is, to exclude competitors. This standard was known as the “scope of the patent” analytic framework – and it’s clearly deferential to reverse payments. Other courts disagreed, notably the 3rd Circuit in the In Re: K-Dur Antitrust Litigation in 2012, which characterized these settlements as presumptively illegal ("prima facie evidence of an unreasonable restraint of trade"). A classic Circuit split developed over the the antitrust analysis applicable to these settlements. The question presented: 
Whether reverse-payment agreements are per se lawful unless the underlying patent litigation was a sham or the patent was obtained by fraud (as the court below held), or instead are presumptively anticompetitive and unlawful (as the Third Circuit has held). 
The FTC urged the Court to adopt a presumptive illegality standard (relying on Section 1 of the Sherman Act) – but the Court has now rejected that in favor of the “rule of reason” analysis under antitrust law – essentially, a contextual inquiry that will study the market, product, parties, etc., to analyze the anticompetitive effects of a particular settlement. This is more of a victory than a loss for the FTC and consumers – because the Court has said that reverse payment settlements are not immune to antitrust scrutiny and any distinct allegations of anticompetitive effect must be considered – albeit against the background of a patent-generated dispute. The FTC reacted accordingly:
The Supreme Court’s decision is a significant victory for American consumers, American taxpayers, and free markets. The Court has made it clear that pay-for-delay agreements between brand and generic drug companies are subject to antitrust scrutiny, and it has rejected the attempt by branded and generic companies to effectively immunize these agreements from the antitrust laws. With this finding, the Court has taken a big step toward addressing a problem that has cost Americans $3.5 billion a year in higher drug prices. 
The lower courts will have to sort out how to assess an antitrust claim apart from a fully litigated patent infringement suit – and Justice Breyer did not provide much of roadmap to do so (now an antitrust analysis must be performed that need not be dependent on litigating the merits of the underlying patent lawsuit, which may be difficult): 
We therefore leave to the lower courts the structuring of the present rule-of-reason antitrust litigation.
Because reverse payment deals delay the entry of generics, it’s been argued that they contravene the spirit of Hatch-Waxman – and now, the Court has authorized the validity of an antitrust inquiry into these settlements. More litigation will follow, and it’s likely that some of these deals will be deemed anticompetitive – and illegal. The result will likely be that brand names will lose a handy mechanism to buy off generic competition. Because generic competition lower drugs prices significantly, consumers are likely to encounter more competitive drug pricing. The Court’s decision may also mean that the appetite for these deals is decreased, as brand name companies consider whether to risk an antitrust challenge to any of these settlements. Alternatively, the deals offered to the generics may not be as lucrative, to avoid triggering the antitrust scrutiny that the Court will now allow.

June 14, 2013

BRCA1 and BRCA2 Genetic Testing Field Expanding Rapidly After Invalidation of Myriad Gene Patents

Within a day of the Supreme Court’s decision in AMP v. Myriad, invalidating patent claims to isolated genes (see here), the genetic testing environment for the BRCA1 and BRCA2 genes has shifted noticeably. Before elaborating on that, it’s worth noting some of the characterizations of the decision from the mainstream press, which reveals public perception of the issues and/or significance of the case. Soon after the opinion was released, the Drudge Report shouted “You Can Keep Your Genes” – a type of headline that appeared in other forms around the country – a mistaken impression that patent rights in human genes translated to any ownership of anyone’s person or bodily materials. But in the sense that the “in vitro” BRCA1 and BRCA2 genes could not be used without permission of the patent holder, the headline had some accuracy. Other news accounts noted the bifurcated nature of the decision, invalidating patents on isolated genes, while upholding patent claims to semi-synthetic cDNA molecules, creating a mixed picture for biotech companies, depending on business models (e.g., genetic testing for single genes or producing recombinant proteins?).

Several companies have announced their intention to offer BRCA1 and BRCA2 testing: in the day since the ruling, DNA Traits has already posted “Proud to Bring BRCA1 and BRCA2 Testing to You” on their website; other go-aheads include Quest Diagnostics, Ambry Genetics and GeneDx, which announced “its intention to launch a suite of comprehensive genetic tests for inherited cancers including BRCA1 and BRCA2 genes, given the Supreme Court's ruling in the Association for Molecular Pathology vs. Myriad Genetics case.” Academic researchers are also gearing up, notably Dr. Mary-Claire King of the University of Washington (see here) and Dr. Wayne Grody of UCLA, who noted that his laboratory would also offer tests on other genetic diseases covered by gene patents, such congenital hearing loss, spinocerebellar ataxia and various muscular dystrophies. Reaction from professional organizations that had participated in the case was enthusiastic. From the Association for Molecular Pathology (AMP), lead plaintiff: 
AMP is very pleased with the Supreme Court’s decision in the case. The Court’s decision that human genes are not patentable is a great step forward for the field of molecular pathology, for genomic science, and most important for our patients. We look forward to exciting future advancements in diagnostic testing and therapeutics that will accrue to the benefit of our patients and our field. 
The American Medical Association (AMA), which filed an amicus brief) reacted: 
The AMA is pleased that the justices saw through the flawed premise that resulted in Myriad’s exclusive patent awards and affirmed that human genes are products of nature and not patent eligible. Removing the patents on the building blocks of life ensures that scientific discovery and medical care based on insights into human DNA will remain freely accessible and widely disseminated, not hidden behind a vast thicket of exclusive rights.  
The College of American Pathologists (CAP) noted the significance for advances in genetic testing:
Genomic medicine has the potential to be a cornerstone of medical testing, treatment, and clinical integration, but the question of ‘who owns your genes’ needed a definitive answer. Now we have it. 
International reaction includes efforts to push for the amendment of the Patent Act in Australia to prohibit gene patents, following a February court decision in that country that had upheld Myriad patent claims against a patentable subject matter-type challenge from Cancer Voices Australia. Testing access is not the only issue at stake in the gene patent controversy. Myriad Genetics, in establishing itself as the central provider and repository for U.S. genetic testing for the BRCA1 and BRCA2 genes, did not maintain a reliable, accessible database of all the mutations in these genes that it had collected over the years. The Sharing Clinical Reports Project, a public effort to get patients and physicians to report genetic mutations to a public database, was announced in April, 2013. The loss for Myriad of its gene patent claims will certainly accelerate the efforts to establish a credible, dynamic BRCA1 and BRCA2 database which is critical for identifying the sites of genetic mutations, their frequency, and the associations between mutations and diagnosis or prognosis. It’s fair to say, at this point, that the BRCA1 and BRCA2 field is now supercharged as a result of yesterday’s decision, and will rapidly correct for the lag and underdevelopment that it has experienced in the nearly 20 years since the first Myriad patents issued.

June 13, 2013

Unanimous Supreme Court Invalidates Gene Patents; Genetic Testing Options Will Expand

Today, the Supreme Court ruled that isolated human genes are not patentable. The case is Association for Molecular Pathology v. Myriad Genetics, a challenge to gene patenting based on the patentable subject matter doctrine of 35 U.S.C. 101. Plaintiffs argued that isolated human genes are natural products which cannot be patented, and that Myriad Genetics' patents on the BRCA1 and BRCA2 (breast cancer) genes were thus invalid. U.S. patent law denies patents for products or laws of nature ("laws of nature, natural phenomena, and abstract ideas are not patentable"). Today’s unanimous opinion was written by Justice Thomas.  Most centrally, the opinion states that Myriad’s patent claims to isolated genes fall within the product of nature and law of nature exceptions to patentable subject matter – as a result, they are invalid. In the ongoing debate over whether genes are simply chemicals or genetic repositories of information (see here), the Court clearly chose the genetic characterization: 
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. Instead, the claims understandably focus on the genetic information encoded in the BRCA1 and BRCA2 genes. 
The Court further noted that “[Myriad’s] claim is concerned primarily with the information contained in the genetic sequence, not with the specific chemical composition of a particular molecule." I have argued that this is the most relevant characterization to considering the patent eligibility of genes (and did so in the amicus brief that I filed in at the Court). In resolving the issue of whether an actual invention was present, the Court did not find Myriad's work to be inventive, in contrast to the work that produced a genetically engineered bacterium in Diamond v. Chakrabarty
In this case, by contrast, Myriad did not create anything. To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention. 
This absence of invention was fatal: 
We merely hold that genes and the information they encode are not patent eligible under §101 simply because they have been isolated from the surrounding genetic material. 
The opinion is helpful in reiterating that discovery and invention are not identical, which is a point that many of us had argued: 
Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry.
The Court rejected any deference to the U.S. Patent and Trademark Office’s issuance of patents on isolated genes, noting that Congress had not spoken to the issue and that the executive branch itself was divided, with the U.S. Solicitor General arguing against the patenting of isolated genes. In holding that isolated genes are not patentable, the Court did hold that cDNAs (complementary DNA molecules with exons left in and introns removed) are patentable because they are not naturally occurring; that aspect of the decision will be important for biotech applications using cDNA to produce recombinant proteins (such as pharmaceuticals or gene therapy). In a broader sense, this decision now enters the lineage of patent decisions from the Supreme Court that squarely define the limits on patentable subject matter, but it's also one more opinion that does not elaborate in detail on any required line-drawing. The decision is a reaffirmation that natural subject matter may not be patented - but it contains no shortcuts to defining "products of nature" or "laws of nature" - undoubtedly leading to further eligibility disputes.

This landmark decision invalidates Myriad’s patent claims to the isolated BRCA1 and BRCA2 genes – an outcome which will open up the genetic testing options for patients for the BRCA1 and BRCA2 genes, expand the research opportunities for scientists, and provide physicians with more diagnostic options than they currently have. The constricted clinical climate created by Myriad’s patents have taken a demonstrable toll on the development of the genetic testing field for the BRCA1 and BRCA2 genes, and this clinical field has not enjoyed a competitive testing environment, in contrast to other clinically significant cancer-related genes. That should change quickly, and clinical developments in the BRCA1 and BRCA2 field should rapidly accelerate. Already, researchers (including Dr. Mary-Claire King, whose pioneering research first established a genetic basis for some breast cancers) are declaring that they will expand their testing portfolio to include BRCA1 and BRCA2 gene testing. The consequences of this decision are very real for women who seek BRCA1 and BRCA2 testing in order to determine if they have a high risk of early onset breast and/or ovarian cancer: more testing choices, coupled with likely lower testing costs in a competitive marketplace. The decision now renders all patent claims to isolated genes invalid, using the logic of the opinion, and this outcome will remove a key patent-related obstacle to the progress of clinical genetics.

June 12, 2013

Federal Circuit: Organic Farmers Cannot Litigate Potential Patent Infringement from Trace Contamination by Patented Seeds

The Federal Circuit has issued its opinion in Organic Seed Growers and Trade Association (OGSATA) v. Monsanto, a declaratory judgment (DJ) action in which OGSATA and other plaintiffs (growers, seed selling businesses, and agricultural organizations) sought to litigate the question of whether inadvertent contamination of their crops by patented Monsanto (GE) seeds could give rise to a potential patent infringement claim by Monsanto. The threshold issue for the plaintiffs has been to establish standing for the suit, relying on their assertions that the prospect of infringement litigation from Monsanto has caused them to limit or halt their farming activities. In 2012, the lower federal court ruled that the plaintiffs could not meet the threshold showing for sustaining a DJ action, and dismissed the case. In the appeal to the Federal Circuit, the oral argument focused on determining whether a “substantial controversy between parties having adverse legal interests of sufficient immediacy and reality" – as required by the Supreme Court in Medimmune v. Genentech (2007) – exists. If so, a DJ action allows the plaintiffs to ask a court to adjudicate whether inadvertent contamination rises to the level of patent infringement, and whether the Monsanto patents are invalid under numerous patent law doctrines. Because patent infringement is generally regarded as a strict liability tort (intention irrelevant), passive contamination of an agricultural field by a patented product could be characterized as a patent infringing use. The plaintiffs argued that their concern over future litigation was warranted by Monsanto’s legal actions to date (between 1997 and 2010, 144 suits and 700 settlements related to unauthorized use of patented seed) and by Monsanto’s refusal to grant the plaintiffs a covenant not to sue. However, Monsanto did make representations of disinterest in pursuing patent infringement claims for instances of trace contamination, such as those contemplated by the plaintiffs. In response to a direct question from the court in oral argument, counsel for Monsanto agreed that representations in the court regarding the lack of the company’s intention to sue for trace contamination might give rise to judicial estoppel for plaintiffs to rely on later. From the opinion:
Taken together, Monsanto’s representations unequivocally disclaim any intent to sue appellant growers, seed sellers, or organizations for inadvertently using or selling “trace amounts” of genetically modified seeds…..We conclude that Monsanto has disclaimed any intent to sue inadvertent users or sellers of seeds that are inadvertently contaminated with up to one percent of seeds carrying Monsanto’s patented traits. 
According to the Federal Circuit, those representations effectively extinguished the claim of legal threat by the plaintiffs: 
In sum, Monsanto’s binding representations remove any risk of suit against the appellants as users or sellers of trace amounts (less than one percent) of modified seed. The appellants have alleged no concrete plans or activities to use or sell greater than trace amounts of modified seed, and accordingly fail to show any risk of suit on that basis. The appellants therefore lack an essential element of standing. 
The Federal Circuit was quite clear in characterizing the nature of Monsanto's representations that plaintiffs had no basis for apprehension:
While Monsanto’s representations are not a covenant not to sue, they have a similar effect. If we rely on Monsanto’s representations to defeat the appellants’ declaratory judgment claims (as we do), those representations are binding as a matter of judicial estoppel. 
In response to the ruling, OGSATA has stated that “we’re encouraged by the court’s determination that Monsanto does not have the right to sue farmers for trace contamination.” For the plaintiffs, the failure to establish a declaratory judgment action also means that their allegations of the patent invalidity of a number of Monsanto patents will not be heard (e.g., contentions that the patents lacked utility under 35 U.S.C. 101). Plaintiffs may appeal to the Supreme Court (which recently considered the patent exhaustion doctrine in the context of patented genetically engineered seeds in Bowman v. Monsanto; see here).

June 3, 2013

Supreme Court: DNA Collection from Arrestees is Constitutional

Today, the Supreme Court issued its opinion in Maryland v. King, a constitutional challenge to Maryland’s statute authorizing DNA collection from those arrested for a “crime of violence, an attempted crime of violence, a burglary, or an attempted burglary.” Maryland processes the DNA sample obtained from an arrestee and uses it for identification by comparing it to DNA profiles held in the federal DNA database, CODIS. In addition to storing offender profiles, CODIS contains DNA profiles from crime scene samples, so the comparison of a DNA sample to those from unsolved crimes might yield a “hit” on an otherwise cold case. The collection of DNA from arrestees has expanded to 28 states and the federal government (with most statutes restricting collection to those accused of felonies or violent crimes). When King was arrested on a assault charge, his DNA was taken and his profile compared to those of unsolved crimes. It matched an unsolved rape case from years earlier (and others), and King was charged with rape (and convicted). His legal challenge alleged that the warrantless and suspicionless search accomplished by his DNA collection at arrest violated a reasonable expectation of privacy, and thus King’s 4th Amendment rights (see here). The court ruled that the practice does not violate the 4th Amendment's prohibition against unreasonable searches and seizures. The 5-4 opinion was written by Justice Kennedy: 
In light of the context of a valid arrest supported by probable cause respondent’s expectations of privacy were not offended by the minor intrusion of a brief swab of his cheeks. By contrast, that same context of arrest gives rise to significant state interests in identifying respondent not only so that the proper name can be attached to his charges but also so that the criminal justice system can make informed decisions concerning pretrial custody. Upon these considerations the Court concludes that DNA identification of arrestees is a reasonable search that can be considered part of a routine booking procedure. When officers make an arrest supported by probable cause to hold for a serious offense and they bring the suspect to the station to be detained in custody, taking and analyzing a cheek swab of the arrestee’s DNA is, like fingerprinting and photographing, a legitimate police booking procedure that is reasonable under the Fourth Amendment.  
The basis for claims that a reasonable expectation of privacy is violated by the DNA collection has encompassed both the collection procedure and the state's access to a DNA profile of the accused. Pivotal to these challenges is how the reasonable expectation of privacy is defined for a particular claimant – parolee, arrestee, etc. Challenges to DNA profiling of those convicted of crimes have largely failed, with courts defining and relying on a diminished expectation of privacy held by parolees, probationers, and now, arrestees. Here, as in earlier DNA cases, the Court did not consider the actual procurement of the sample by cheek swab to be intrusive. With respect to the claim of privacy to the DNA profile itself, the Court noted that “while science can always progress further, and those progressions may have Fourth Amendment implications” and that “the argument that the testing at issue in this case reveals any private medical information at all is open to dispute,” it followed the general consensus that the 13 short tandem repeat (STR) sites used in DNA profiling are not generally informative beyond establishing identification. It further noted that the authorizing statute prohibits the use of DNA profiling for purposes other than identification: 
In light of the scientific and statutory safeguards, once respondent’s DNA was lawfully collected the STR analysis of respondent’s DNA pursuant to CODIS procedures did not amount to a significant invasion of privacy that would render the DNA identification impermissible under the Fourth Amendment. 
The ruling will likely undermine challenges to the constitutionality of other state DNA collection statutes authorizing collection at arrest. What certainly lies ahead will be deeper scientific insight into the human genome, such that previously uncharacterized regions of the genome will be characterized as revealing medically or physically informative attributes of the individual (see here). To the extent that the forensic sites of interest (currently the 13 CODIS STR sites) are further annotated by genomic science, one part of the constitutional argument alleging a privacy violation will be strengthened by claims that medically revealing information could be obtained. However, it is still likely that a court could rely on the statutory limitations to the uses for a DNA profile in finding that 4th Amendment safeguards are sufficient. The practical implication of today’s rulings are immediately apparent: likely, more states will expand their DNA collection practices to include arrestees. An increased ability to solve crimes with high recidivism is likely, as advocates of arrestee DNA testing and advocates for sexual assault survivors have argued (and with particular force for sexual assault crimes, where serial crime patterns have been established through crime scene sampling (even decades-old), but for which no perpetrator identity has yet matched to a series of profiles. The ruling particularly impacts efforts to reduce violence against women. The City of Chicago conducted a study on preventable crimes in 2005, concluding that DNA sampling on arrest could have prevented at least 53 murders and rapes committed by those with multiple (and unprofiled) felony arrests (similar results were reported in a study by the Denver District Attorney).

May 30, 2013

More GINA Enforcement: EEOC Files Genetic Discrimination Class Action

The Equal Employment Opportunity Commission (EEOC) has filed its first class action lawsuit, EEOC v. Founders Pavilion, alleging violations of the Genetic Information Nondiscrimination Act (GINA), which took effect in 2009. GINA applies to two separate spheres, health insurance (Title I) and employment (Title II). Under Title II of GINA, it is illegal to discriminate against employees or applicants because of genetic information. In this legal action, the EEOC has sued Founders, Inc., a Corning, N.Y., nursing and rehabilitation center. In the complaint filed last week, the EEOC alleges that Founders: 
(1) requires a class of applicants and employees to provide genetic information in response to questions about family medical history, in violation of GINA, (2) terminated two individuals it regarded as disabled, and terminated one disabled individual after failing to provide her a reasonable accommodation during her probationary period, all in violation of the ADA, and (3) refused to hire one woman, withdrew an offer of employment to a second woman, and terminated a third woman because they were pregnant, in violation of Title VII. 
This lawsuit originates from the violation of three separate statutes enforced by the EEOC: GINA, American with Disabilities Act (ADA), and Title VII of the Civil Rights Act of 1964. This is the second GINA enforcement action announced by the EEOC this month (see here). This newly filed case has overtones of an earlier pre-GINA lawsuit from 1998, Norman Bloodsaw v. Lawrence Berkeley Laboratory, alleging multiple civil rights claims based on the employment practices of a federal research laboratory. The 9th Circuit upheld findings that the laboratory had conducted unlawful surreptitious medical testing of and discriminated against employees in violation of the ADA, Title VII, and both the federal and state (California) constitutional rights to privacy. With respect to genetic testing, the courts found that the laboratory had conducted unauthorized testing for sickle cell trait, a genetically based condition, and the 9th Circuit found that practice unconstitutional under the general privacy protections afforded by the 4th Amendment: 
One can think of few subject areas more personal and more likely to implicate privacy interests than that of one's health or genetic make-up. 
Norman-Bloodsaw reached unauthorized genetic testing through constitutional privacy claims in a pre-GINA era; surreptitious genetic testing in the workplace has also been captured using ADA violations. This month’s actions from the EEOC signal its seriousness about utilizing GINA to limit excessive probing of genetic medical information from applicants or employees, an aspect of the statute that, until now, was likely less appreciated (or observed) than the more prominent prohibition of adverse workplace treatment of employees based on their genetic status (discrimination in the form of failure to hire, differential treatment or termination).

May 23, 2013

FDA Continues Approvals of Companion Diagnostics for Pharmacogenetic Cancer Treatment

The regulation of genetic tests is uneven, with the FDA exercising enforcement discretion of this field within its general authority to regulate medical devices. To date, the FDA requires approval of genetic testing kits, considered to be in vitro diagnostics (IVD). The FDA has paid specific attention to one subset of genetic test kits, known as companion diagnostics. The FDA describes companion diagnostics: 
A companion diagnostic device can be in vitro diagnostic device or an imaging tool that provides information that is essential for the safe and effective use of a corresponding therapeutic product. The use of an IVD companion diagnostic device with a particular therapeutic product is stipulated in the instructions for use in the labeling of both the diagnostic device and the corresponding therapeutic product, as well as in the labeling of any generic equivalents and biosimilar equivalents of the therapeutic product.
Companion diagnostics illustrate the use of pharmacogenetics to refine pharmaceutical treatment of cancers or other illnesses. The FDA has just approved a new companion diagnostic test for use in the treatment of non small cell lung cancer, the cobas EGFR Mutation Test that refines the optimal use for Tarceva, a biotech drug approved by the FDA in 2004 (a monoclonal antibody). This approval scenario illustrates how the optimal treatment profile for an already approved drug is being refined by subsequent genetic research, where new understandings of the relationship between particular genes and the specific cancers is allowing for more refinement in treatment decisions. The FDA published a guidance document for the approval of companion diagnostics in 2011: 
An IVD companion diagnostic device could be essential for the safe and effective use of a corresponding therapeutic product to identify patients who are most likely to benefit from a particular therapeutic product; identify patients likely to be at increased risk for serious adverse reactions as a result of treatment with a particular therapeutic product; or monitor response to treatment for the purpose of adjusting treatment (e.g., schedule, dose, discontinuation) to achieve improved safety or effectiveness. 
The FDA also recognizes a scenario of co-development between a drug manufacturer and a test developer, such that both products are approved simultaneously, as illustrated by the FDA's co-approval of Xalkori and the Vysis ALK Break Apart FISH Probe Kit in 2011. The list of approved companion diagnostics continues to grow. As a general matter, the FDA regulates genetic tests sold as kits to laboratories or consumers. In the general genetic testing market, however, most genetic tests are offered as laboratory-derived tests (LDTs), available as services, rather than products. The FDA does not regulate LDTs, although it has stated that some LDTs are considered medical devices, subject to its oversight. However, despite issuing a statement of intention for possible oversight in 2010, the FDA to date has not taken on LDTs in general, or even the genetic LDTs. Laboratories providing LDTs are regulated under the Clinical Laboratory Improvement Amendments (CLIA), administered by the Centers for Medicare and Medicaid Services (CMS), which requires that laboratories meet specified standards, and that individual tests are scientifically accurate, but which does not evaluate the clinical validity or clinical utility of LDTs. Calls for the FDA to increase its involvement in the regulation of LDTs have come from many sources, including the Secretary's Advisory Committee for Genetics, Health and Society in 2008. More recently, the American College of Medical Genetics published a risk-classification framework for the regulation of LDT genetic tests, calling for FDA pre-market approval of high-risk LDTs, where "the consequence of an incorrect result or interpretation could lead to serious mortality or morbidity."

May 14, 2013

Bowman v. Monsanto: Supreme Court Interprets Patent Exhaustion for Genetically Engineered Seeds

Yesterday, the Supreme Court issued its opinion in Bowman v. Monsanto, a patent infringement case that tested how the doctrine of patent exhaustion applies to self-replicating patented inventions such as genetically engineered (GE) seeds. The patented invention is the Monsanto Roundup Ready soybean, which contain a gene that encodes EPSPS, a glyphosate-tolerant enzyme. The genetically modified plants express the enzyme and thus exhibit resistance to the herbicide glyphosate– specifically, to the application of the Monsanto glyphosate product, sold as Roundup. A license restriction accompanies the sale of the Roundup Ready seeds, and it prohibits the use of second-generation seeds in later plantings. Farmer Vernon Bowman was accused of patent infringement by buying GE commodity seed from a grain elevator (not directly from Monsanto) which he then used for replanting (replication); Monsanto characterized his activities as an unauthorized use of a patented invention because it involved the “making” of a patented article. The doctrine of patent exhaustion operates to limit the control that an inventor holds over the life of a lawfully sold patented article – the first sale of a patented invention is authorized, and that act exhausts the control that the patent holder retains over subsequent uses of the article (absent some valid conditional sale agreement that accompanies the sale). Did that doctrine extend to a claim that a later sale of originally-patented GE seed to Bowman and his use in planting became an act of patent infringement because the seed replicates and he “made” an infringing article? In 2011, the Federal Circuit ruled that Bowman’s planting of the GE seed he purchased became an act of patent infringement, rejecting an interpretation of the exhaustion doctrine that would recognize the special attributes of seeds, which embody the property of replication and “manufacture” of an originally-patented invention (see earlier post). Did the company’s patent rights extend to this later series of events, or did they exhaust upon the first sale of the patented seed? Although one can freely “use” a product after patent exhaustion, does that authorize a use that results in the creation of a new copy of the patented article, which is generally viewed as an act of patent infringement? In the unanimous opinion authored by Justice Kagan, the Supreme Court said no: 
Reproducing a patented article no doubt “uses” it after a fashion. But as already explained, we have always drawn the boundaries of the exhaustion doctrine to exclude that activity, so that the patentee retains an undiminished right to prohibit others from making the thing his patent protects. 
What does not exhaust is the ability of patent holder to enforce one of the rights of exclusion, that is, the ability to prevent unauthorized replication of a patented invention. No exception applied here to GE seeds in this scenario, despite Bowman's invocation of self-replication by the product itself. Justice Kagan did note, however, that the decision was limited to this set of facts:
Our holding today is limited—addressing the situation before us, rather than every one involving a self-replicating product. We recognize that such inventions are becoming ever more prevalent, complex, and diverse. In another case, the article’s self-replication might occur outside the purchaser’s control. Or it might be a necessary but incidental step in using the item for another purpose. 
This restraint from the Court at least references analogous scenarios in computer software, where use of a lawfully obtained program often requires the making of a copy on a host computer; Congress has address this with an amendment to copyright law (17 U.S.C. 117) that immunizes users from copyright infringement in such circumstances. There is some pushback in Congress with respect to patented seeds and the restrictions that accompany their sale; H.R.19, the Seed Availability and Competition Act of 2013 was introduced this year and it authorizes second generation plantings of patented seeds, effectively establishing a compulsory license, but setting a royalty mechanism for payments to the patent holder. This is unlikely to garner significant support in Congress, but it indicates that there are legislative approaches that can theoretically modulate patent rights for certain technologies, if the political will exists to do so.

May 12, 2013

USDA to Heighten Environmental Review for New Herbicide-Resistant Genetically Engineered Crops

The U.S. Department of Agriculture's Animal and Plant Health Inspection Service (APHIS) has announced this week that it will heighten its regulatory review for the possible introduction of the next wave of herbicide-resistant genetically engineered (GE) crops. Using its authority under the Plant Protection Act, APHIS regulates genetically engineered crops because it has determined that they may pose a risk as plant pests. Companies seeking to introduce a new crop to market file an application for deregulated status with APHIS. In this case, the applications seeking APHIS deregulation are for Dow Chemical’s corn and soybeans genetically engineered for resistance to the herbicide 2,4-D and Monsanto’s cotton and soybeans genetically engineered for resistance to dicamba. In addition to compliance with the Plant Protection Act, APHIS must also comply with the National Environmental Policy Act (NEPA)
Under the National Environmental Policy Act, APHIS is required to evaluate the potential environmental impacts from a "major Federal Action" - that can include the deregulation of new GE plants by the Agency. If APHIS finds that its potential regulatory decision may significantly affect the quality of the human environment, the Agency must prepare an EIS (environmental impact statement) before making a decision on the proposed Federal action. 
APHIS had prepared a draft environmental assessment for the crops in the Dow petition. Petitions for deregulation of these crops (which would allow commercial release) had been submitted to APHIS and published for public comments; APHIS noted that significant numbers of comments had been received. APHIS has thus concluded: 
With regard to these new herbicide-resistant plants, through its analysis of information submitted by the developers, as well as public comments, APHIS has determined that its regulatory decisions may significantly affect the quality of the human environment. APHIS therefore believes it necessary under NEPA to prepare these two EIS's to further assist the Agency in evaluating any potential environmental impacts before we make a final determination regarding the products' regulatory status.
Several points are worth noting about the APHIS decision and the larger debate over the use of genetically engineered crops (which are largely engineered for agronomic, not dietary purposes). In contrast to several other proposed deregulations over the last several years (alfalfa, sugar beets), where APHIS did not conduct an EIS, and was sued for noncompliance with NEPA, here APHIS is triggering an EIS of its own accord. The use of genetically engineered glyphosate-resistant crops (most famously, Monsanto Roundup Ready corn, soybeans) since the 1990’s led to extensive litigation over how APHIS managed its NEPA requirements; ultimately, judicial action compelled APHIS to prepare an EIS, and it then deregulated the crops. In the decade or more since the Roundup approach to weed management, glyphosate-resistant weeds have emerged, thus undermining the viability of this strategy for weed containment. Debate continues over whether successive waves of genetic engineering related to designated herbicides will adequately provide effective weed management (one research group describes an “accelerated transgene facilitated herbicide treadmill”). Criticism is also directed at the environmental consequences from the use of the herbicides; litigation against the Environmental Protection Agency attempted to rescind its approval of 2,4-D. However, it is notable that APHIS specifically cabins the focus of the EIS:
While the EIS’s will look more broadly at potential impacts to the environment as a whole, APHIS’ regulatory authority is based on The Plant Protection Act and the Agency’s oversight is specific to evaluating the potential for the GE plants to pose a plant pest risk to crops or other plants. 
While technically true, APHIS is also charged by NEPA with an evaluation that considers how a “potential regulatory decision may significantly affect the quality of the human environment.” The decision by APHIS suggests that the agency might have anticipated immediate litigation if it had not prepared an EIS, and due to the delays that previous cases have imposed, may have decided that direct preparation of an EIS was more efficient. That, of course, does not predict the outcome of the EIS. However, it will take place against the backdrop of some of the limitations to genetically engineered weed management that have been revealed by earlier containment strategies.

May 8, 2013

GINA Enforced: EEOC Settles Its First Genetic Discrimination Lawsuit

The Equal Employment Opportunity Commission (EEOC) has announced a settlement in what it describes as the first lawsuit it has filed alleging genetic discrimination in violation of the Genetic Information Nondiscrimination Act (GINA), enacted in 2008. GINA applies to two separate spheres, health insurance (Title I) and employment (Title II) (see here). From the EEOC
Under Title II of GINA, it is illegal to discriminate against employees or applicants because of genetic information. Title II of GINA prohibits the use of genetic information in making employment decisions, restricts employers and other entities covered by Title II (employment agencies, labor organizations and joint labor-management training and apprenticeship programs - referred to as "covered entities") from requesting, requiring or purchasing genetic information, and strictly limits the disclosure of genetic information. 
In this case, the EEOC charged that Fabricut, Inc., an Oklahoma wholesale distributor of home furnishing items, violated GINA’s general prohibition on obtaining genetic information from an applicant or employee; it then denied employment based on the results. GINA defines genetic information broadly:
Genetic information includes information about an individual’s genetic tests and the genetic tests of an individual’s family members, as well as information about the manifestation of a disease or disorder in an individual’s family members (i.e. family medical history). Family medical history is included in the definition of genetic information because it is often used to determine whether someone has an increased risk of getting a disease, disorder, or condition in the future. Genetic information also includes an individual's request for, or receipt of, genetic services, or the participation in clinical research that includes genetic services by the individual or a family member of the individual, and the genetic information of a fetus carried by an individual or by a pregnant woman who is a family member of the individual and the genetic information of any embryo legally held by the individual or family member using an assisted reproductive technology. 
Here, an individual who was offered a position with Fabricut was required to take a pre-employment (post-offer) medical exam, during which her family medical history was compiled, in violation of GINA. Based on this history and testing performed by its contract medical examiner, the company told the newly hired employee that she needed to be evaluated for carpal tunnel syndrome (CTS), a type of neuropathy that can result in muscle weakness and a marked inability to perform repetitive tasks (and which can have a genetic component). The employee’s own doctor concluded she did not have CTS, but the company nonetheless rescinded her job offer. In the consent decree, Fabricut will pay $50,000, in addition to undertaking “the posting of an anti-discrimination notice to employees, dissemination of anti-discrimination policies to employees and providing anti-discrimination training to employees with hiring responsibilities.” The lawsuit had also alleged a violation of the American with Disabilities Act (ADA) in that its failure to hire the employee was based on the fact that she was “regarded as” having a disability, in violation of the statute (the ADA also has guidelines on when medical exams can be required in the workplace in general). In 2001, the EEOC reached a settlement with Burlington Northern Santa Fe Railway over the misuse of genetic information under the ADA, where the company attempted to deny disability payments by surreptitious genetic testing of its employees for susceptibility to CTS. At the time, GINA did not exist, and the ADA was used to capture what resembled genetic discrimination in the absence of a more directed statute. Now, GINA exists, and the EEOC can charge genetic discrimination directly. The statistics on genetic discrimination complaints filed with the EEOC for 2012 reveal that of the 280 GINA charges investigated by the EEOC, approximately 59% found no reasonable cause, while approximately 13% did find reasonable cause. The trendline shows an increase in GINA complaints every year. Although many employers are aware of GINA and the general prohibition against genetic discrimination, the Fabricut case will further emphasize how employers must steer clear of collecting genetic information in the course of otherwise legitimate employment-related medical exams, and how GINA builds on the ADA protections for employees or applicants against extraneous medical inquiries by employers.

April 25, 2013

Avian Influenza A(H7N9): Full Genetic Sequence Publicly Available

The avian influenza A(H7N9) virus (official name) has emerged in China since February, and human cases of infection have increased steadily and spread to Taiwan. Of 112 cases reported, there are 22 deaths; China Daily updates; map of cases here. Just yesterday, the World Health Organization (WHO) issued this characterization: “This is an unusually dangerous virus for humans," said Keiji Fukuda, assistant director-general for health security of WHO. The true pathogenicity of the virus in humans is unclear; some reports state a mortality rate of 20% (deaths/cases); however, this is inexact because there may be mild disease that is not detected, and the actual lethality may be lower. The virus is avian in origin, a triple reassortant (mixture) of three avian viruses. Initial assessments are that humans are acquiring infection through contact with infected birds; the unanswered question is whether human-to-human transmission is occurring (a precursor to a true pandemic). H7N9 has been sequenced and genetic analysis reported by two groups, one from China and one an international collaboration, which noted: “These viruses possess several characteristic features of mammalian influenza viruses, which are likely to contribute to their ability to infect humans and raise concerns regarding their pandemic potential.” Since the outbreak originates from China, the level of transparency from this country is critical and so far, reports are positive. WHO has reported that it receives case notifications from Chinese public health officials, and that China has sent virus samples to all 5 international collaborating centers for influenza (which includes the U.S. Centers for Disease Control (CDC)).The virus genetic sequences (sequences of the coding regions of all eight viral genes) were deposited in the influenza sequence database maintained by the Global Initiative on Sharing All Influenza Data (GISAID). This is a global consortium that was started after the 2004-5 influenza A(H5N1) outbreaks, amid concerns that virus sequences were not being shared, due to concerns about asymmetry between virus sharing and access to antivirals and vaccines, particularly from developing countries (e.g., Indonesia withheld H5N1 viruses). Claims for patent rights surfaced in the H5N1 pandemic, including a patent application filed by the CDC (see here for my article on the set of patent rights relevant to influenza pandemics). Despite the fact that patent rights have been sought for H5N1 virus sequences and H1N1 virus sequences, the sensibility of GISAID is to encourage unrestricted access: 
Influenza viruses have not been subject to intellectual property rights historically. This tradition has been important because the required changes in influenza viruses contained in human influenza virus vaccines to match those viruses circulating currently in the field must occur at a speed far in excess of the legal process associated with the attainment of commercial protection. In order to allow rapid development of products such as vaccines and other interventions on an equitable basis by all countries and other interested parties, the convention has been for human health professionals to share virus specimens and data openly without creating barriers of exclusivity such as the filing of patents. 
Already, this public health crisis illustrates a strikingly different posture by China in contrast to its reaction to the emergence of SARS (Severe Acute Respiratory Syndrome) in 2003, most notably in transparency. During that period, China was not initially forthcoming with the details of the epidemic, and the absence of information impeded public health surveillance. When SARS appeared, the causative agent was not immediately known and it was finally identified as a novel coronavirus. In addition to the difficulties on obtaining actual epidemiological data during the crisis, the SARS crisis was also encumbered by the efforts of leading research groups to file patent applications on the SARS virus sequence. With respect to influenza viruses in general, progress in linking the sharing of virus genetic sequences to access to countermeasures (overcoming some of obstacles in the H5N1 pandemic) has occurred with the establishment in 2011 of the Pandemic Influenza Preparedness Framework Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits (PIP) by WHO, which applies to influenza viruses with pandemic potential. PIP thus encourages the dissemination of virus samples and research results; it also provides for transparency in virus sequence tracing by contributing laboratories, and it embeds norms which discourage seeking intellectual property rights (but this is not legally binding). As PIP is recently enacted, it has yet to be tested in a declared pandemic, and it is not clear that the current H7N9 outbreaks will amplify into an official pandemic. 

One other aspect of H7N9 is notable at present: the virus genetic sequence has two mutations linked to increased human-to-human transmission which were identified in the H5N1 research papers that were subject to debate in late 2011 as possible sources of dual-use information (the debate centered on whether the data should be published). For background, see here and here. The question: what does the observation of these mutations mean for the viability (and scientific merit) of the earlier dual-use experiments? Has their utility been increased as a result of what is being learned about H7N9? 

April 16, 2013

Supreme Court Oral Argument on Gene Patents in AMP v. Myriad

Yesterday, the Supreme Court heard oral arguments in Association for Molecular Pathology v. Myriad Genetics, in which a coalition of patients, physicians and researchers challenged the validity of Myriad’s patents on the BRCA1 and BRCA2 genes (see here and here). The challenge is based on 35 U.S.C. 101 (patentable subject matter), and it asserts that isolated human genes are natural products which cannot be patented because U.S. patent law denies patents for products or laws of nature. That prohibition is grounded in the Court’s own jurisprudence, which distinguishes “between products of nature, whether living or not, and human-made inventions” (Diamond v. Chakrabarty, 1980). I attended the oral argument, having filed an amicus brief, and here is an initial overview. Counsel for the Petitioners, AMP et al., advanced the importance of the product of nature doctrine in disqualifying patents on genes, and responded to questions on multiple issues: how could DNA patenting could be distinguished from other kinds of drug patents, would a biotech company have an incentive to isolate genes if patents are not available, and whether cDNA, which Justice Kennedy labeled an “economy-class gene,” differed enough from a native gene to be patentable. In an ongoing attempt to frame gene patenting in a more familiar context, the Justices utilized several analogies to genes during the session, from an Amazon plant-derived drug, to a baseball bat excised from a tree, to the ingredients in chocolate chip cookies. The U.S. government, represented by the Solicitor General, emphasized that the product of nature doctrine was essential to maintain a boundary between freely available, unpatented scientific phenomena, and inventive efforts that can be patented, and argued that patents on genes violate that doctrine. He reiterated the government’s view that cDNAs, as “artificial DNA” were patent-eligible, while unmodified genomic DNA was not. The appearance from the executive branch highlights the split on the issue of gene patenting between the Justice Department and the Patent and Trademark Office (PTO), which has granted gene patents for several decades. 

Counsel for the Respondent, Myriad, confronted questions regarding how an isolated gene differs from a native gene, and a query from Justice Kagan that probed the limits of patent eligibility: “Do you think that the first person who isolated chromosomes could have gotten a patent on that?  Counsel conceded that “it would pass through the Section 101 gate.” Justice Breyer responded to that hypothetical: “Everything is inside something else. Plants, rocks, whatever you want. And so everything will involve your vast taking something out of some other thing where it is, if only the environment. And it's at that point that I look for some other test than just that it was found within some other thing.” Breyer indicated, therefore, that mere extraction alone could not provide a meaningful test for eligibility, and it produced an open-ended 35 U.S.C. 101 with no limits: “[W]e are reducing, then, 101 to anything under the sun, and -- and that, it seems to me, we've rejected more often than we've followed it.” Breyer could certainly been referring to Mayo v. Prometheus (2012), in which the Court invalidated a patent on methods of optimizing drug dosage (in an opinion that he authored). Although respondents raised the issue of industry reliance on gene patents, and urged deference to PTO guidelines that implement the policy of granting patents on genes, Justice Ginsburg noted the disapproval of the PTO's view within the executive branch (“even though the Government has disavowed it”) and she concluded that “the strength of the presumption" of deference would be diluted. Several recurring themes emerged. Questions regarding the eligibility of cDNA comprised a good part of the session, with several Justices seeking to answer how a decision that invalidated isolated genes, but upheld cDNAs would be received by the biotech industry. The focus on cDNA indicates that the Court is trying to define the scope of its decision, and it could indicate that the Court is not struggling over the central issue of the patent eligibility of the isolated gene. On another point, the Justices were concerned with whether and how patents for the methods attendant to the discovery of a new natural molecule (e.g., method of isolation, method of tagging, method of use) might provide enough incentives for investment even if a patent on the molecule could not be obtained. It did not appear that the Court was persuaded that enough differences exist between native genes and isolated genes to survive the prohibition on patenting products of nature. It did appear that the Court might be receptive to the respondents’ and the government’s argument that enough structural and functional differences between native genes and cDNA molecules exist to render the latter patentable, and a decision upholding only the cDNA patent claims might appeal to the Court. Importantly, such an outcome would still affirm the product of nature doctrine. However, if the Court can further clarify the legal analysis for that doctrine, it would be useful for biotechnology in general, as this case presents a rare opportunity for the Court to do so.

April 7, 2013

Alaska Continues Statewide Opposition to FDA Approval of Genetically Engineered Salmon

At state and federal levels, Alaska continues to display its opposition to the introduction of a genetically engineered (GE) food product - specifically, to the potential entry of GE salmon into the U.S. marketplace (see here). To date, the product, AquAdvantage salmon, made by AquaBounty Technologies (ABT) has not received market approval from the FDA. To produce the GE salmon, Atlantic salmon is engineered to contain the growth hormone gene from Pacific Chinook salmon, which causes the fish to grow in less time; the gene is placed under the control of a promoter from ocean pout, which causes elevated expression of the hormone. According to ABT, the addition of the growth hormone gene “provides the fish with the potential to grow to market size in half the time of conventional salmon.” At the end of 2012, pursuant to the National Environmental Policy Act (NEPA), the FDA released a draft Environmental Assessment (EA) in support of its Finding of No Significant Impact (FONSI) for AquAdvantage salmon. The FONSI determination, if prevailing, means that the FDA will not be required to prepare the more rigorous environmental impact statement (EIS) for GE salmon; this determination has been criticized by consumer advocates. The FDA has extended the period for public comments on the draft EA until April 26, 2013. Both state and federal legislators from Alaska have been active in opposing the introduction of the fish, voicing concerns about potential mating between the GE salmon and the native Alaska salmon, with the potential for irreversible genetic contamination of the wild-type stock. According to ABT, the selected fish would be female and sterile and could not breed with the wild salmon. But assuming less than 100% ability to properly screen and control the stocks, even a minute number of GE fish that could breed into the wild population could initiate the genetic contamination of the wild-type stock. The Alaska legislature has now passed a bipartisan resolution opposing the introduction of the GE salmon
Opposing the United States Food and Drug Administration's preliminary finding relating to genetically engineered salmon; urging further examination of genetically engineered salmon; opposing AquaBounty's petition to produce genetically engineered salmon; and proposing, if AquaBounty's petition is approved, that its product should be labeled as "genetically modified.” 
The regulatory paradigm for the review of the ABT salmon is that the added gene is reviewed as a veterinary drug: "the rDNA construct in the resulting GE animal is thus a regulated article that meets the drug definition" - hence the oversight by the FDA's Center for Veterinary Medicine (CVM). In 2010, an earlier CVM report stated that there were no significant safety or environmental issues raised by the ABT salmon. A food additive petition was filed at the FDA by food safety advocates in 2012, requesting that the addition of the growth hormone gene to the fish trigger a food additive review, bringing the GE salmon under the purview of a more conventional food safety review process. In addition, current FDA policy will not require the GE salmon to be labeled (nor any other GE food). Several supermarket chains have announced that they will not carry the GE salmon product. Just last month, Sen. Mark Begich (D-AK) succeeded in introducing an amendment to the continuing resolution passed in March (temporary budget agreement) that would establish a reserve fund for the labeling of GE fish. Begich also introduced two bills in the Senate; a prohibition on approval of GE salmon (the bill cites “escapement”) and, if GE salmon is approved, a requirement for food labeling (that would a first at the federal level). Regarding the strength of the opposition in Alaska, there is no comparable statewide cohesion to date targeting a specific GE food product. More generally, future litigation is likely to challenge both the FDA’s regulatory paradigm for GE salmon as well as the merits of the FONSI determination for the food product by the agency.