The movement to place a referendum on the ballot in Colorado this year that would authorize the labeling of foods with genetically engineered (GE) ingredients has survived a legal challenge by opponents. Initiative 48 has been submitted by Right to Know Colorado GMO, which must now collect 86,105 signatures needed for the measure to appear on the 2014 Colorado ballot. A challenge to the proposed referendum was filed by an association of retail grocers, alleging that the measure was “misleading.” That petition recited various misleading aspects of the ballot measure, including this allegation:
The titles do not inform voters that the essence of the Proposed Initiative is that the failure to label genetically modified food is treated as "misbranding" of food.
In an order issued by the Colorado Supreme Court, the court affirmed an earlier decision of the Title Board, which characterized the initiative in its brief to the court:
The meat of the initiative is not misbranding. It is the creation of new labeling responsibilities to inform consumers.
If Right to Know Colorado can submit enough signatures for the ballot, it will appear later this year. In general, state-level developments in the labeling of genetically engineered food or ingredients emerge through direct legislative enactments (see here) or by ballot measures (see here). Many state-level legislative attempts to require GE labeling have failed (such as this effort in Colorado last year), so the direct ballot route becomes an alternative. That, however, is no guarantee of electoral success (a mandatory GE food labeling referendum, Proposition 37, appeared on the California 2012 ballot, and was defeated). In fact, defeat of that referendum has swung the pendulum back to a direct legislative effort in California this year (supporters note that “SB 1381 is a simpler, clearer version of Prop. 37).”
In a long-awaited opinion issued yesterday in Haskell v. Harris, the en banc 9th Circuit has upheld the constitutionality of the California law that authorizes the collection and testing of DNA samples from all persons arrested for or charged with any felony or attempted felony (profiles are entered into the national CODIS database). The practice of collecting DNA from arrestees began in Louisiana in 1997. The recent trend in state DNA collection practices for law enforcement has been to expand DNA profiling from those convicted of crimes to those arrested for various crimes. The Supreme Court upheld the constitutionality of arrestee DNA collection against a 4th Amendment challenge in Maryland v. King (2013) (see earlier post). California’s expansion of its DNA database was initiated with the passage of Proposition 69 in 2004, and expanded to include arrestees in 2009. An earlier 9th Circuit panel upheld the practice in 2012, while a state court disagreed and found the practice unconstitutional. In yesterday's ruling, Judge M. Smith filed a concurrence that accompanied the terse per curiam opinion from the full panel, acknowledged the impact of King:
The Supreme Court’s decision in King is fatal to Plaintiffs’ claims.
The court did note some of the safeguards in California’s policy (and which are found in most state policies):
Only law enforcement officials may access a DNA profile, and they may only use the DNA for identification purposes. Id. §§ 295.1(a), 299.5(f). Unauthorized access or disclosure is punishable under state law by imprisonment and a criminal fine. Id. § 299.5(i). Federal law imposes similar penalties for unauthorized use of, or access to, CODIS. See 4 2 U.S.C. §§ 14133(c), 14135e(c). An arrestee who is not ultimately convicted may ask the trial court to order the sample destroyed and the DNA profile expunged. Cal. Penal Code § 299(b).
This case took an interesting twist in 2012, when scientists in the ENCODE project published more annotation of the human genome and the development invited an analysis that the genetic markers used in forensic DNA science were more informative (and thus the collection was more invasive) than law enforcement claimed (see submission to the court by the Electronic Frontier Foundation and earlier post). There is no mention of the ENCODE-based arguments in the opinion just released. In its amicus brief, the Obama administration sided with California in arguing for the constitutionality of the law.The 9th Circuit opinion signals that 4th Amendment challenges to arrestee DNA collection are unlikely to succeed in view of King. It's possible that more detailed annotation of the human genome might provide a basis for future arguments that the CODIS markers are more informationally revealing than is currently believed (thus altering the privacy calculus), but the 9th Circuit's ruling ignored the opportunity to opine on the relevance of evolving science, leaving that to future cases.
The U.S. Patent and Trademark Office (PTO) has issued patent examination guidelines that reflect the impact of two recent Supreme Court patent decisions in the life sciences on the question of what constitutes patent-eligible subject matter. These cases challenged the Court to engage in line-drawing at the boundaries of patentable subject matter ("laws of nature, natural phenomena, and abstract ideas are not patentable"). In Mayo v. Prometheus (2012) , the Court invalidated a patent on methods of optimizing drug dosage, deciding that the patent claims had the effect of preempting a law of nature (a natural correlation). In last year’s AMP v. Myriad opinion, the Court invalidated patent claims to isolated genes on the basis that they fell within the product of nature and law of nature exceptions to patentable subject matter. Now, the PTO has issued guidelines for examiners to determine whether a patent claim differs enough from what exists in nature and thus is eligible, or whether a claim is effectively drawn to something that is naturally occurring. A three-part analysis is provided:
Question 1: Is the claimed invention directed to one of the four statutory patent-eligible subject matter categories: process, machine, manufacture, or composition of matter? If no, the claim is not eligible for patent protection and should be rejected under 35 U.S.C. 101, for at least this reason. See MPEP § 706.03 for a description of the appropriate form paragraphs to use in rejecting the claim. If yes, proceed to Question 2.
Question 2: Does the claim recite or involve one or more judicial exceptions? If no, the claim is patent-eligible, and the analysis is complete. If yes, or if it is unclear whether the claim recites or involves a judicial exception, proceed to Question 3.
Question 3: Does the claim as a whole recite something significantly different than the judicial exception(s)? If the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
The Guidelines provide more elaboration of factors that can be applied to the “significantly different” analysis. What’s noteworthy is that neither Supreme Court case, from which the Guidelines follow, used an explicit “significantly different” framework to sort the eligible from the ineligible. Actual touchstones for analysis from the Court include whether a law of nature is “preempted” by a patent claim or whether a natural product is more than merely “isolated” from the surrounding environment. However, the lineage of the new formulation can be traced back to Diamond v. Chakrabarty (1980):
[T]he patentee has produced a new bacterium with markedly different characteristics from any found in nature.
The new Guidelines call for an examiner to consider whether the claim includes features or steps that demonstrate that the claimed subject matter exhibits a marked difference from what exists in nature (and the focus is on structure, not function). The Guidelines do reveal that the PTO interprets the force of the AMP decision to apply to all manner of natural products and substances, not just nucleic acids (DNA):
In particular, claimed subject matter that must be analyzed under Question 3 to determine whether it is a natural product includes, but is not limited to: chemicals derived from natural sources (e.g., antibiotics, fats, oils, petroleum derivatives, resins, toxins, etc.); foods (e.g., fruits, grains, meats and vegetables); metals and metallic compounds that exist in nature; minerals; natural materials (e.g., rocks, sands, soils); nucleic acids; organisms (e.g., bacteria, plants and multicellular animals); proteins and peptides; and other substances found in or derived from nature.
There was little doubt that the rationale for the Court’s rejection of the Myriad gene patent claims could easily be extended to all manner of natural products, and the Guidelines confirm that. Yet this expansive view could be litigated down the line, as proponents of patent claims on isolated products could try again to revive the Parke-Davis v. Mulford (1911) reasoning to argue commercial and therapeutic transformations of a natural product as a basis for patent eligibility (actually a more function-oriented argument). I don’t think this strategy will prevail, ultimately, but the life science-wide implications of the very recent AMP decision are not likely to go unchallenged.
The FDA is considering the merits of an assisted reproductive technology (ART) that has a goal of eliminating the transmission of genetically based mitochondrial diseases. Mitochondria, small DNA packages in the cytoplasm of the cell, are inherited in the maternally-provided egg during reproduction. For women who could transmit mitochondrial disease to offspring, this ART protocol involves the production of an altered egg, which has the nuclear DNA of the mother swapped into the egg of a woman without the genetic disease. Thus the egg is a genetic hybrid. Conventional in vitro fertilization (IVF) follows the manipulation of the egg. This technique has been dubbed "3-parent babies" because the child would inherit DNA from 2 females and one male. Is it safe? In the U.S., the FDA halted the use of a fertility treatment involving cytoplasmic transfer in eggs that was used in 2001, asserting its authority to regulate this technique as part of its ongoing supervision of the production and use of biologic products (e.g. cells, tissues, etc). Although technically genetic material is swapped around in order to “delete” the disease-causing genes, this is not quite the genetic engineering often imagined in which the nuclear genetic material would be deleted, supplemented or rearranged (”designer genes).” In fact, cellular structure makes this technique quite conceptually simple as the mitochondria are cellular organelles that exist outside the nucleus, facilitating a replacement scheme such as the one here. An Oregon scientist, Dr. Shoukhrat Mitalipov, has published experiments documenting success with the use of the technique in monkeys and would like to begin the use of the technique in humans. He would need FDA approval to begin any clinical trials in humans. In two days of open public hearings this week, the Cellular, Tissue, and Gene Therapies Advisory Committee of the FDA invited testimony from scientists and other commenters regarding the scientific, technical and clinical concerns for the use of mitochondrial manipulation technologies. They described their task:
The committee will discuss oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or treatment of infertility.
The FDA asserts its authority over the use of this technique as deriving from its role in regulating the production and use of biologic materials, from its ongoing review of protocols that involve genetic manipulation, as well as its goal of insuring the safety of human study subjects. In a briefing document prepared for the hearings, the committee cited a long list of potential safety concerns for both mother and child from the use of the mitochondrial replacement technique:
Potential risks to the women could include: 1) failure to become pregnant; 2) failure to deliver a child; 3) risks associated with the specific mitochondrial manipulation technology procedure; and 4) toxicities of the reagents used in mitochondrial manipulation technologies. Potential risks to their children could include: 1) mitochondrial disease (particularly in women with mitochondrial disease), as a result of carryover of abnormal mitochondria and heteroplasmy; 2) disorders due to nuclear mitochondrial incompatibility; 3) disorders related to aberrant epigenetic modifications ; 4) birth defects and other disorders associated with the specific mitochondrial manipulation technology procedure; and 5) toxicities of reagents used in mitochondrial manipulation technologies. There may be additional risks that are difficult to predict because of limitations in current knowledge.
The FDA will receive public comment on a draft guidance it has issued to those designing protocols for early-phase clinical trials with such techniques. The public comment period closes May 9, 2014. Although fertility clinics in the U.S. are not subject to extensive oversight from the FDA or any other agency, this proposed ART technique comes under FDA purview by its use, manipulation and transfer of biologic products into humans. Effectively, and critically, this technique is a germ-line modification of an embryo, meaning that the genetic manipulation will be carried into future offspring which inherit the replaced mitochondria. That fact heightens the concerns over the safety and ethical dimensions of potential use. Germline modification of embryos is prohibited in at least 40 countries, and there has been a kind of international consensus against use of these techniques. However, in a sign that a more nuanced regulation of certain ARTs may be developing, the UK is also considering whether to approve this use of this ART.
The FDA continues to monitor the emerging field of stem cell medicine, which offers the possibility of treating certain medical disorders by the application of new cells which replenish deteriorating tissues (e.g., Parkinson’s, heart disease, diabetes). The prospect of harvesting a patient’s own stem cells and administering them to sites of cellular stress is a new paradigm for disease treatment (autologous stem cell therapy). Nonetheless, such practices challenge existing legal regimes which regulate the introduction of pharmaceutical and biologic products into the marketplace. Regenerative Sciences, Inc., is a Colorado corporation that its Regenexx stem cell treatment, offered to patients suffering from a number of musculoskeletal conditions. The procedure involves withdrawing bone marrow from a patient, extracting the mesenchymal stem cells from the marrow, and processing the cells to create a therapeutic preparation for injection to a site of interest, with a goal of restoring function to impaired joints. Since 2008, the FDA has cautioned the company that its practice was likely violating the Federal Food Drug and Cosmetic Act (FDCA) because it involved the use of an unapproved drug and likely violating the a biological product under the Public Health Service Act (PHSA), because it used an unapproved biologic product. The FDA also inspected the Regenerative facilities in 2009, and found numerous departures from good manufacturing practices. The FDA then sued to enjoin the company from offering unapproved stem cell treatments and prevailed in federal district court in 2012. The court granted summary judgment on a motion by the FDA that the Regenerative stem cell preparation was both a drug and a biologic, and, as such, was both adulterated and misbranded, in violation of both statutes (see earlier post). The court issued a permanent injunction against Regenerative, prohibiting it from offering the stem cell treatment.
Now, the D.C. Circuit has upheld the district court’s decision, rejecting the defendant’s arguments that it was simply engaged in the practice of medicine, which is not regulated by the FDA, and is governed by state law. The appellate court affirmed the lower court’s finding that the stem cell preparation was both a “drug” and a “biologic” and required FDA approval before use in clinical medicine, noting that these existing laws do not interfere with the practice of medicine:
Appellants’ construction of the FDCA, by contrast, would allow states to gut the FDCA’s regulation of doctors, and thereby create an enormous gap in the FDCA’s coverage, by classifying the distribution of drugs by doctors as the practice of medicine. Given Congress’s intent that the FDCA’s “coverage be as broad as its literal language indicates," United States v. An Article of Drug . . .Bacto-Unidisk, 394 U.S. 784, 798 (1969), such a construction is not tenable.
Critics of these FDA enforcement activities argue that the application of the standard drug approval process to stem cell therapies (especially with the use of autologous cells harvested from the patient) undercuts innovation in the field. Proponents of FDA regulation argue that existing statutory responsibilities call for the agency to monitor the use of stem cell therapies, yet some concede that the use of autologous stem cell therapies calls for a novel regulatory policy that is especially tailored to these procedures, rather than the application of “one size fits all” FDCA and PHSA requirements.
