November 30, 2015

FDA Approves Genetically Engineered Salmon for Market; No Labeling Required

The FDA has issued an approval for the marketing of genetically engineered (GE) Atlantic salmon, capping a long regulatory review (see here). The product, AquaAdvantage, made by Aqua Bounty, Inc., has been under agency review for years. This Atlantic salmon has been genetically engineered to add the growth hormone gene from the Chinook salmon, which causes the fish to reach market weight in about half the time. The FDA regulates GE animals under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) because recombinant DNA introduced into an animal is treated as a drug. From the FDA statement
Based on a comprehensive analysis of the scientific evidence, the FDA determined that AquAdvantage Salmon meets the statutory requirements for safety and effectiveness under the Federal Food, Drug, and Cosmetic Act. Among the requirements the sponsor had to meet are that food from the fish is safe to eat; the rDNA construct (the piece of DNA that makes the salmon grow faster) is safe for the fish itself; and the AquAdvantage Salmon meets the sponsor’s claim about faster growth. In addition, the FDA determined that food from AquAdvantage Salmon is as safe to eat and as nutritious as food from other non-GE Atlantic salmon and that there are no biologically relevant differences in the nutritional profile of AquAdvantage Salmon compared to that of other farm-raised Atlantic salmon.

The AquAdvantage Salmon may be raised only in land-based, contained hatchery tanks in two specific facilities in Canada and Panama. The approval does not allow AquAdvantage Salmon to be bred or raised in the United States. In fact, under this approval, no other facilities or locations, in the United States or elsewhere, are authorized for breeding or raising AquAdvantage Salmon that are intended for marketing as food to U.S. consumers. As required by the National Environmental Policy Act, the FDA completed an environmental assessment to determine whether approval of the application would result in significant effects on the quality of the human environment in the United States. The FDA has determined that the approval of the AquAdvantage Salmon application would not have a significant environmental impact because of the multiple and redundant measures being taken to contain the fish and prevent their escape and establishment in the environment.
The agency will not require the GE salmon to be labeled:
Based on our assessments of food derived from the AquAdvantage Salmon, we have determined that the term “Atlantic salmon” is the appropriate common or usual name for such food within the meaning of section 403(i) of the FD&C Act because AquAdvantage Salmon meets FDA’s regulatory standard for Atlantic salmon (Ref. 10) and the composition and basic nature of food from AquAdvantage Salmon does not significantly differ from its non-GE counterpart—non-GE farm-raised Atlantic salmon. In addition, we have determined that food derived from AquAdvantage Salmon is as safe and nutritious as food from other farm-raised Atlantic salmon. For these reasons, we have concluded that there is no material difference between food derived from AquAdvantage Salmon and food derived from other non-GE, farm-raised Atlantic salmon that is required to be disclosed in the labeling of food derived from AquAdvantage Salmon under the relevant provisions of the FD&C Act, as explained above. See 21 U.S.C. 321(n) & 343(a).
Senator Lisa Murkowski (R-AK) has been an outspoken opponent of FDA approval of the GE salmon (in line with general statewide opposition), and has been attempting to pass legislation requiring the labeling of the GE salmon if the agency approval cannot be overturned:
The FDA has said there will be draft guidance on voluntary labeling indicating whether food has or has not been derived from GE Atlantic salmon. So, basically, if you want to put a label on that says this is a fake fish, a fake salmon, you can go ahead, but you don't have to. It is only voluntary. That is not good enough for this mom. That is not good enough for most who care about what their families are eating. So we are going to continue to press for mandatory labeling if the FDA is going to approve--wrongheadedly, in my mind--this genetically engineered fake fish for human consumption. They darn well better agree that labeling will be required because I am not going to eat it. 
Public sentiment against approval of the GE salmon was well-registered with the FDA; over 1.5 million public comments were posted against agency approval; the agency decision not to require labeling has generated more opposition and the FDA's safety evaluation has been challenged as cursory. The marketplace could well determine whether GE salmon actually becomes part of the American food supply; many retailers and restaurants are on record stating that they will not sell the product. Upcoming developments to watch will be the ongoing pressure to require labeling (as well as the Senate prospects for the federal anti-GE labeling bill discussed here earlier). Furthermore, the fate of future GE seafood products (about 35, by one count) that come before the FDA remains uncertain. Lastly, a lawsuit has been filed in Canada opposing the AquaBounty production of the GE salmon eggs in Canada as a potential environmental threat to wild salmon stocks.

November 16, 2015

Federal Circuit Considers Rehearing on Denial of Patent to Noninvasive Prenatal Testing of Fetal DNA

Non-invasive prenatal testing (NIPT) is an alternative to the invasive techniques of amniocentesis or chorionic villi sampling used in reproductive medicine, both of which carry some risk to the fetus. The research demonstrating that fetal DNA could be recovered from maternal serum prompted the development of testing techniques that could simply rely on maternal blood testing in order to recover fetal DNA and perform genetic analysis. The scientists were awarded U.S. Patent No. 6,258,540. Claim 1 of the patent: 
A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises amplifying a paternally inherited nucleic acid from the serum or plasma sample and detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample. 
Sequenom, Inc. holds the rights to the patent. It sued Ariosa Diagnostics and several other genetic testing companies for infringement of the patent. In Ariosa Diagnostics, Inc. v. Sequenom, Inc., issued in June, the Federal Circuit ruled that the patent claims to methods for detecting and recovering the fetal DNA from a maternal sample were invalid for lack of patentable subject matter (35 U.S.C. § 101) (see here). That decision followed a sequence of recent Supreme Court cases, AMP v. Myriad (2013) (Myriad) and Mayo v. Prometheus (2012) (Mayo) that each invalidated patent claims in the life sciences for a lack of patentable subject matter. The Federal Circuit relied on the analytic framework from Mayo to dissect the patent claims, summarizing the test as follows: 
First, we determine whether the claims at issue are directed to a patent-ineligible concept. If the answer is yes, then we next consider the elements of each claim both individually and “as an ordered combination” to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. 
The court noted that the presence of fetal DNA in maternal serum was a patent- ineligible natural phenomenon (step 1) and then proceeded to step 2, where it considered whether any other elements of the patent claim (detecting, amplifying) operated to transform the unpatentable natural phenomenon: 
Thus, in this case, appending routine, conventional steps to a natural phenomenon, specified at a high level of generality, is not enough to supply an inventive concept. Where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent eligible subject matter if the methods themselves are conventional, routine and well understood applications in the art. The claims of the ’540 patent at issue in this appeal are not directed to patent eligible subject matter and are therefore, invalid. 
Judge Linn filed a concurrence, but made it clear that he did so because Mayo demanded the application of a fairly unforgiving test that led to an incorrect result in this case. In August, Sequenom filed a petition with the Federal Circuit requesting a rehearing en banc, contending that the panel’s decision wrongly applied the Mayo framework to find a groundbreaking invention unpatentable (see here): 
To avoid this absurd result, all the Court must do is reaffirm—as did the Supreme
Court in Mayo—that a combination of known steps that incorporates or is motivated by an unpatentable natural phenomenon is nonetheless patentable if that combination “considered as a whole” was not routine before the patent disclosed it.
Sequenom then described the future impact of the decision as "an existential threat:" 
The full Court's intervention is particularly necessary because, if this Court does not step in and draw this line, the panel's rule threatens to swallow many more meritorious inventions along with this one. 
Ariosa has recently filed its response to the Sequenom petition. Ariosa argues that the Federal Circuit’s decision properly utilized the Mayo-based framework as an analytic device:   
Appellants’ only legal argument (as opposed to their dire policy-based prognostications) in favor of rehearing en banc is that Mayo, Myriad and Diehr must be read as teaching that “a combination of known steps that incorporates or is motivated by an unpatentable natural phenomenon is nonetheless patentable if that combination ‘considered as a whole’ was not routine before the patent disclosed it.” Yet Appellants’ misreading of those precedents amounts to nothing short of a wholesale revision of the Supreme Court’s two-part test for determining whether a claim recites patent-eligible subject matter.   
The contrasting arguments of the parties frame a question for the Federal Circuit regarding whether a patent claim embedding a natural phenomenon requires a holistic interpretation (Sequenom) or should be subject to a more splintered analysis (Ariosa). A decision from the Federal Circuit on the petition for rehearing is likely to issue in the next several months; if they do not accept it, the decision could then be appealed to the Supreme Court, which has issued two life science decisions on patentable subject matter in the last three years.

November 6, 2015

ASHG Recommends State Licensure of Genetic Counselors

The medical specialty of genetic counseling is high in demand these days as genetically-informed medical care (genomic medicine, precision medicine) becomes the dominant paradigm in heath care. The National Society of Genetic Counselors (NSGC) provides the following definition of the field:
Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates:
Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence. 
Education about inheritance, testing, management, prevention, resources and research. 
Counseling to promote informed choices and adaptation to the risk or condition. 
To date, about 20 states require genetic counselors to be licensed for practice (here is the Pennsylvania licensing law). The U.S. has a generally state-based model of professional licensure for medical occupations (M.D.s included). Now, the American Society of Human Genetics (ASHG), a primary professional organization in clinical genetics, has called for state licensure of genetic counselors across the U.S. From the ASHG statement:
Healthcare reform and the rapidly expanding role of genomics in many healthcare decisions will increase the demand for qualified genetics professionals. State licensure of certified counselors will help to ensure that the healthcare system has a qualified workforce to provide genetic and genomic services for the  growing number of patients and families who need them.
Many health plans recognize genetic counselors as important members of the healthcare team and depend on them to help ensure provision of state-of-the art genetic services, including the ordering of  appropriate genetic/genomic tests and the attendant pre-and post-test counseling and education. Licensure also provides genetic counselors with the credentials many hospitals need to approve billing and reimbursement for services. 
ASHG supports licensure already enacted by more than twenty states and encourages the remaining states to license certified genetic counselors as one way to increase access to high-quality  genetic/genomic services across the country. 
The NSGC has published model legislation for licensure. The ASHG’s recent recommendation in favor of state licensure signals the increasing need for standardized professional services, albeit with state variations (e.g., see earlier post on Virgina's licensure statute). At least five states have licensing legislation pending. A parallel observation on the trend toward genetic counseling licensure is to note that the services of such professionals are often incorporated into patient management by referral from treating physicians; however, some studies suggest that genetic counselors are actually underutilized in some sectors of genetic testing (see here and here), with the consequence that patients undergoing such testing may not receive optimal education and guidance about their test results.