Federal Circuit Schedules Rehearing of Gene Patent Challenge

Today, the Federal Circuit has released its schedule for the rehearing of the gene patent litigation, Association for Molecular Pathology v. U.S. Patent and Trademark Office (AMP v. USPTO), in which a coalition of physiicans, researchers and patients brought a declaratory judgment action against Myriad Genetics, Inc., alleging that its patent claims to the isolated BRCA1 and BRCA2 genes as well as its methods for genetic testing were not patentable subject matter under 35 U.S.C. 101. After the district court handed down its decision in 2010, invaliding both types of patent claims, Myriad appealed to the Federal Circuit (I filed an amicus brief, available here). The 2011 Federal Circuit decision affirmed the invalidation of the method claims, but ruled that the isolated DNA claims were patentable subject matter. An appeal then went to the Supreme Court, which now had two pending biotechnology patentable subject matter cases in its docket for the first time since Diamond v. Chakrabarty in 1980 (in which the Supreme Court upheld a patent on a genetically engineered bacterium). In the interim, the Supreme Court decided Prometheus v. Mayo (Mayo) which presented the issue of whether patent claims to a method of drug treatment which utilized a metabolic relationship to formulate drug dosages violated the long-standing prohibition against patenting laws of nature. In the opinion authored by Justice Breyer, the court decided that the method claims were not patentable subject matter: “To put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well-understood, routine conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. The Court described the practical burden that invalid or overly broad patent claims place on the general enterprise of innovation: “that very exclusivity can impede the flow of information that might permit, indeed spur, invention, by, for example, raising the price of using the patented ideas once created, requiring potential users to conduct costly and time-consuming searches of existing patents and pending patent applications, and requiring the negotiation of complex licensing arrangements.” Instead of taking on the merits of AMP v. USPTO, the Court then granted certiorari, but vacated the judgment and remanded the case back to the Federal Circuit for reconsideration in light of its Mayo decision. Today's Order asks the parties and amici to address the following issue: “What is the applicability of the Supreme Court’s decision in Mayo to Myriad’s isolated DNA claims and to method claim 20 of the ’282 patent?” The rehearing in AMP v. USPTO will now center squarely on the disputed patent claims to the isolated genes, with the Supreme Court's reaffirmation of two key points from Mayo providing context: the distinctness of the patentable subject matter doctrine and the integrity of the well-established patenting limits. Additionally, these product (composition of matter) patent claims must now be analyzed using the perspective provided by the Court's analysis of the method claims in Mayo. The Federal Circuit has scheduled the new oral argument in AMP v. USPTO for July 20, 2012.

Maryland Court Strikes Down DNA Collection from Arrestees

The Maryland Court of Appeals has handed down a 5-2 decision in which it has declared that the collection of DNA from arrestees by state law enforcement officials is unconstitutional. The decision struck down the Maryland DNA Collection Act, which took effect in 2009, and expanded DNA collection to include those arrested for crime of violence, a attempted crime of violence, a burglary, or an attempted burglary. This ruling is at odds with two recent decisions from federal appellate courts which considered separate 4th Amendment challenges to DNA collection from arrestees. 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 Harris v. Kamala, the 9th Circuit upheld the California state law that authorized DNA collection from arrestees. These cases generally balance an asserted reasonable expectation of a right to privacy in DNA (arguing the general standard from Katz v. U.S.) and invoke a general 4th Amendment requirement of reasonable suspicion and probable cause to counter the argued need of law enforcement to obtain and use the DNA information in "non-individualized" manner. There can be two aspects of privacy in the DNA collection: the question of the collection procedure (generally, a cheek swab) and the separate question of the privacy interest in the genetic information provided by laboratory processing (currently not a full genomic readout, but only the use of FBI/CODIS standard of 13 genetic loci. Against these interests, the government typically argues the compelling state interest in solving crimes, viewed against the backdrop of procedural safeguards in these laws (expungement if no conviction, secure databases, minimal genetic information revealed). The Supreme Court denied a petition for certiorari in Mitchell (challenge to federal DNA collection statute); whether the Court will later take up an arrestee challenge to a state DNA collection law (as in this case) is unclear. At the nationwide level. the state DNA databases, at this point in 2012, generally mandate the inclusion of those convicted of felonies, at the very least, and may extend to lower level offenses, depending on the state; efforts continue to expand the databases to include arrestees.

Legal Challenge to NIH Funding of Stem Cell Research Continues

The ongoing litigation that challenges the Obama administration policy on the funding of human embryonic stem cell (hESC) research continues this week, as the Court of Appeals for the D.C. Circuit heard arguments in the case. The debate over such funding occurs against the backdrop of the long-existing Dickey Wicker amendment which prohibits the use of federal funds for any research in which an embryo is destroyed. The lawsuit against NIH, brought by several adult stem cell researchers, allege that the federal funding sponsored by the Department of Health and Human Services (HHS) and the National Institutes of Health (NIH) violates this existing funding prohibition. This funding followed the 2009 Obama Executive Order, which ended the Bush-era hESC funding ban. The current NIH Stem Cell Guidelines make note of the Dickey-Wicker funding restrictions, but reach the conclusion that its funding of hESC research does not violate them: "These guidelines therefore recognize the distinction, accepted by Congress, between the derivation of stem cells from an embryo that results in the embryo’s destruction, for which federal funding is prohibited, and research involving hESCs that does not involve an embryo nor result in an embryo’s destruction, for which federal funding is permitted." The guidelines dictate the proper sources for hESC: “hESCs derived from embryos created using in vitro fertilization (IVF) for reproductive purposes and no longer needed for these purposes, assuming the research has scientific merit and the embryos were donated after proper informed consent was obtained from the donor(s).” Thus, NIH is not endorsing the creation of embryos for the purpose of deriving embryonic stem cells, noting that “additional sources of human pluripotent stem cells proposed by the respondents involve complex ethical and scientific issues on which a similar consensus has not emerged.” An amicus brief filed by Coalition for the Advancement of Medical Research (composed of hospitals, universities, and patient advocates) and the Genetics Policy Institute, Inc., urged the court to rule for the legality of the NIH policy. No doubt, more uncertainty over the legal status of hESC research continues the climate of instability in which this research has been conducted, at least since the 2001 Bush administration policy that halted the use of federal funds for the creation of any new hESC stem cell lines. This policy was reversed in 2009 by President Obama, but the current litigation poses a direct challenge to its legality. Nonetheless, in the torturous route this litigation has taken, the fact that, in 2011, the D.C. Circuit had earlier declined to uphold a 2010 preliminary injunction against NIH (partly because of its view of the weakness of the plaintiffs’ case against NIH) would seem to indicate that the court will uphold the legality of the NIH funding policy. Nonetheless, hESC research is a political issue that will be affected by the outcome of the 2012 presidential race; the NIH funding policy is politically dependent on which political party controls the executive branch.

H5N1 Influenza Fallout Continues

More developments have occurred in the wake of the recommendation of the National Science Advisory Board for Biosecurity (NSABB) to endorse publication of two scientific papers which reported the construction of possibly pandemic-potential H5N1 influenza viruses. The full NSABB report has been released and the dissension in the board is noted, including scientific disagreement over the danger of the actual viruses and disagreement over whether the manuscripts were “enabling” and whether publication of the details of the virus were likely to contribute to public health surveillance efforts. There is a nod to the likelihood that similar controversies will reoccur (for example, as the board notes, other “gain-of-function” experiments that introduce new capabilities into influenza viruses). The report states that “the Board also recognizes that research findings will likely emerge in the very near future that should not be widely disseminated because of a high risk of misuse but that nevertheless should be made available to certain researchers and public health officials around the world who have a legitimate need to know.” This suggests that pressure will be brought to establish a dissemination track that can be activated for DURC research (and such a mechanism could allow a broader evaluation of risk than just an NSABB review). Such efforts have been discussed and were particularly resonant in the immediate post-9/11 period (see a report prepared for Congress in 2003, discussing the possibility of using “classified” or “sensitive” designations could invoke publication restraints). For example, in 2005, researchers succeeded in reconstructing the infuenza virus that caused the 1918 pandemic. The NSABB reviewed and endorsed the publication of the reconstructed 1918 influenza virus in 2005, but some reporting from that period is certainly evocative of where we are now: “As part of this process, the Board transmitted several recommendations to Secretary Leavitt: One was that the manuscripts needed modifications to explain the health benefits of the research to the public. Another was the need to amplify the discussion of the measures taken to protect researchers and the public from accidental exposure or inappropriate access to the virus. The Board also recommended the development of additional Federal biosafety guidelines and a Federal regulatory framework for controlling access to the 1918 virus. Subsequent to these discussions, the virus was added to the Select Agent list. Lastly, the Board recommended development of a comprehensive communication plan for public dissemination of this type of information.” Additionally, the recent NSABB recommendations have now been formally accepted by the National Institutes of Health and forwarded to the Secretary of Health and Human Services (the NSABB is advisory to the NIH, which itself is overseen by HHS). And there is more. All of the attention to this newly developed influenza virus emanate from the concern over the “dual-use” character of the research – both useful for medical and scientific purposes, but also susceptible to nefarious use as a bioterrorist agent. Thus, NIH has also conducted a contemporaneous review of possible dual-use research projects and issued a new policy which aims to “establish regular review of United States Government funded or conducted research with certain high-consequence pathogens and toxins for its potential to be dual use research of concern (DURC).” Thus, NIH is signaling that it does not want to be caught by surprise when the next manuscript of concern emerges. The legislative branch is not left out (see earlier story). This week, the Senate Committee on Homeland Security and Governmental Affairs will hold a hearing on government sponsorship of this research and the publication consequences, featuring speakers from both NIH and NSABB. And finally, Representative Sensenbrenner has renewed his demands for more information from NIH regarding the NSABB process, noting that one NSABB member has issued a critique of the review process as not providing an even-handed review of the risks and benefits of publication. 

Genetic Discrimination in Employment: EEOC and GINA

The federal Genetic Information Nondiscrimination Act (GINA) was enacted in 2008, after years of lobbying to get Congress to respond to the emergence of genetic discrimination in employment and access to health insurance. Title I of the law addresses the use of genetic information in health insurance, while Title II prohibits genetic discrimination in the workplace against job applicants and/or employees (and applies to all employers with 15 or more employees). The federal Equal Employment Opportunity Commission (EEOC) is charged with enforcement of Title II of GINA, and also enforces, inter alia, the prohibition of discrimination on the basis of race, color, religion, national origin or sex under Title VII of the 1964 Civil Rights Act, and the protection for disabled individuals under the 1992 American with Disabilities Act (ADA). Prior to GINA, the resolution of claims of genetic discrimination found support in existing constitutional doctrines. In Norman-Bloodsaw v. Lawrence Berkeley Laboratory (9th Circuit, 1998), a case that predated GINA, where employees were subject to surreptitious genetic testing for and subsequent use of genetic information in a racially discriminatory manner, the court sustained claims of 4th Amendment violations as well as violations of the right to privacy under the 14th Amendment and Title VII violations. From the court opinion: "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." In 2002, and also pre-GINA, the EEOC settled the case of genetic discrimination against the Burlington Northern and Santa Fe Railway Company under the ADA. A new EEOC GINA regulation took effect this month that further solidifies the inclusion of GINA into the repertoire of civil rights laws in the workplace, including Title VII and the ADA. Employers subject to GINA must now comply with record-retention requirements as rigorous as those that apply to the enforcement of Title VII and the ADA. These include standard retention periods for all records as well as specific preservation of records that pertain to a charge of discrimination filed under GINA. Recent statistics from the EEOC report that in 2011, of the 211 charges investigated by the EEOC, a quick comparison of outcomes that reflect factual determinations shows approximately 67% found no reasonable cause, while approximately 5% did find reasonable cause. We can expect that the further development of genetic susceptibility data will intersect with the workplace in complicated determinations of causation for claims of workplace-induced injury or disease; GINA will now provide some measure of legal protection where genetic information is either used to screen out job applicants or terminate employees based on genetic status. 

The Science of "Omics:" Regulating Bioinformatic Tests in Medicine

The rapid development of new genetic tests and the expansion of commercial genetic testing reflect the years of molecular research that has uncovered genes, proteins, RNA and metabolites that are implicated in disease processes.  Widely known are, for example, the single gene tests that allow a patient to be tested for a genetic predisposition to disease based on whether she has a mutation in the relevant gene (e.g., BRCA1 testing for breast/ovarian cancer).  But these conceptually simply tests are rapidly being supplemented by the next wave of clinical molecular medicine. The collection of fields now known collectively as “omics” represent molecular science as it now seeks to explain biological phenomena through the collective behavior of multiple genes or proteins (essentially looking for patterns in large datasets). These become the fields of genomics, proteomics, metabolomics, etc. Because of the large data volumes, they lie at the intersection of biotechnology and computer science (i.e., bioinformatics). One commercially available example is the Mammaprint genetic test, which tests 70 genes in a breast cancer patient genes to develop a genetic “signature” that indicates the likelihood of recurrence (and the advisability of further treatment). Such a test requires the collection of accurate biological data accompanied by a computational model that integrates the profile information to arrive at a clinically relevant conclusion. Some of these tests to date have been regulated by the Food and Drug Administration as in vitro diagnostics (IVD), but there is no coherent regulatory scheme for genetic laboratory science that integrates the oversight of single-gene genetic tests with the more complex genetic signature tests. However, due to a recent case at Duke University where a researcher had engaged in the use of faulty gene pattern tests as the basis for decision-making in providing chemotherapy to cancer patients in clinical trials, the National Cancer Institute asked the Institute of Medicine (IOM) to review how “omics” tests are developed, validated and regulated. In the report recently issued, Evolution of Translational Omics: Lessons Learned and the Path Forward, the IOM has called for improvements in the way these "omics" tests are peer-evaluated, but also asks for the developers of such genetic tests to consult with the FDA prior to using such tests in clinical trials.These developments are very significant because we expect that the potential uses of molecular patterns to inform clinical decisions are numerous but potentially susceptible to irregular development and even (unintentional) misuse. The uneven involvement of the FDA in the regulation of genetic testing has contributed to the chaotic environment in which these technologies are entering clinical trials, and later, the marketplace. The real world consequence is that patients could be given faulty clinical information regarding their diagnosis, prognosis or treatment options. While the incentives to produce gene or protein signatures of clinical significance will increase, the consequences of misinformed clinical care are very real. A the IOM report concludes, all of this argues for a institutional culture – government, funders, universities, journals – that appreciate the novel, interdisciplinary nature of these laboratory tests and provide assessments that match their complexity.

9th Circuit Rejects DOJ Challenge to Ruling on Stem Cell Donation

Technological advances can shift the legal characterization of a practice in medical care from prohibited to allowed – the case of compensation for bone marrow donation makes this point. Bone marrow donations are sought by many patients with blood and other disorders who require an infusion of new stem cells that can resupply critical blood types (bone marrow is a rich source of such cells). Typically, this has been done by bone marrow aspiration, where a donor undergoes aspiration of bone marrow directly, later processed for its stem cells; hence the term “bone marrow transplant” was often used. In Flynn v. Holder, the 9th Circuit ruled last December that the modern methods for recovering stem cells from bone marrow now allow for the procedure to be characterized as a kind of blood donation, rather than an organ donation; now, a donor goes to a facility and undergoes a kind of blood filtration to remove stem cells (peripheral blood stem cell apheresis), which is painless and non-invasive. The consequences of this shift are significant in that the the National Organ Transplant Act (NOTA), passed in 1984, prohibits any sale of human organs in interstate commerce. That legislation attempts to frustrate any markets for human organs by criminalizing the payments for human organ donations. In contrast, blood donations are not affected by this prohibition; payments for blood donations are routine. Thus, for the first time, the 9th Circuit ruling allows bone marrow donors to be paid; this has been championed by patient advocacy groups for those need genetically matched bone marrow. Surprisingly, after the ruling in December, Attorney General Eric Holder asked the court to rehear the case en banc (full panel of the 9th Circuit). This has now been denied. According to the court, the government’s argument that “bone marrow” in NOTA was to be understood to apply to the stem cells – however recovered – is not correct. The court has reaffirmed its ruling, and donors may be recruited with financial incentives without running afoul of NOTA. This is a wise decision; the pushback from the Department of Justice might be understood in view of what they may have viewed as a slippery slope toward the introduction of commerce into organ donation, but this apprehension does not require that the law fail to understand when technology really does shift. From the court opinion: 

It may be that “bone marrow transplant” is an anachronism that will soon fade away, as peripheral blood stem cell apheresis replaces aspiration as the transplant technique, much as “dial the phone” is fading away now that telephones do not have dials. Or it may live on, as “brief” does, even though “briefs” are now lengthy arguments rather than, as they used to be, brief summaries of authorities. Either way, when the“peripheral blood stem cell apheresis” method of“bone marrow transplantation” is used, it is not a transfer of a “human organ” or a “subpart thereof” as defined by the statute and regulation, so the statute does not criminalize compensating the donor.