April 16, 2017

UC Berkeley Appeals Adverse CRISPR Genome Editing Patent Interference Decision

A recent inventorship dispute between the University of California at Berkeley (UC) and the Broad Institute at MIT centered on which institution was entitled to patents for the use of CRISPR-Cas9 (CRISPR) genome editing methods in eukaryotic cells (an interference proceeding). In its recent adjudication of the conflict, the United States Patent and Trademark Office Patent Trial and Appeal Board (PTAB) declared no conflicting patent rights between a UC patent application and the already issued patents of MIT; therefore, the existing grant of patents to MIT for the use of CRISPR in eukaryotic cells was upheld, and the UC application for the use of CRISPR in all cells could continue prosecution. In the decision, the PTAB found that the patent claims of the Broad Institute to the use of CRISPR in eucaryotic cells was not obvious in view of the originally filed UC patent application, therefore, the subject matter of Broad did not overlap with that of UC. MIT has already issued patents, while UC's patent application is still pending. Now, UC has announced an intention to file an appeal with the Federal Circuit of the adverse PTAB ruling in February. From the UC press release:
Given the revolutionary nature of the CRISPR-Cas9 technology, UC believes that obtaining a timely confirmation that its scientific team was the first to invent the use of the technology in all environments, including eukaryotic cells, is important for current and potential users of the technology, including academia, industry and the public at large.
 In parallel, UC intends to pursue continuing applications in the U.S. and globally to obtain patents claiming the CRISPR-Cas9 technology and its application in non-cellular and cellular settings, including eukaryotic cells. Corresponding patents have already been granted to UC in the United Kingdom, and the European Patent Office has announced that it will grant UC’s patent on May 10, 2017.
The Broad Institute has issued a statement on the appeal: 
UCB has filed a Notice of Appeal asking the United States Court of Appeals for the Federal Circuit, based in Washington DC, to review the recent decision by the PTAB (Patent Trial and Appeals Board) that there is no interference between the Broad Institute, MIT and Harvard claims concerning the use of the CRISPR system in eukaryotic cells and the patent application of UCB because the claims are patentably distinct.
Given that the facts have not changed, we expect the outcome will once again be the same.
We are confident the Federal Circuit will affirm the PTAB decision and recognize the contribution of the Broad, MIT and Harvard in developing this transformative technology.
The Federal Circuit can review the PTAB ruling for any error or law or lack of substantial evidence, but will defer to the factual findings from the board. If the ruling is left in place, UC can still move ahead with its patent application to the use of CRISPR in all cells. Theoretically, such a UC patent could coexist with the Broad patent to the use of CRISPR in eucaryotic cells. A potential user might then have to seek permission or license from both patent holders to use the CRISPR system in eucaryotic cells. The parties themselves (UC, Broad) might need to seek cross-licensing from each other to utilize CRISPR in eucaryotic cells. While the current dispute centers on the specific and valuable CRISPR-Cas9 system, other permutations of the CRISPR methodology can utilize different enzymes (e.g., CRISPR-Cpf1) and are therefore separately eligible for patenting, unconnected to this particular UC/Broad conflict.

April 9, 2017

FDA Authorizes Marketing of 23andMe Direct to Consumer Genetic Health Risk Tests

The FDA has authorized the marketing of the first direct to consumer (DTC) genetic health risk reports, offered by 23andMe, a California corporation offering genetic testing services. These are their Personal Genome Service Genetic Health Risk (GHR) products. The company describes the tests:
A genetic health risk report offers customers the opportunity to see whether they have genetic variants that increase their chances of developing certain health conditions. Not everyone with a risk variant will develop the health condition. And for most of these conditions, not having a genetic variant does not eliminate the risk of the health condition.
The FDA described the approval of the tests:
The U.S. Food and Drug Administration today allowed marketing of 23andMe Personal Genome Service Genetic Health Risk (GHR) tests for 10 diseases or conditions. These are the first direct-to-consumer (DTC) tests authorized by the FDA that provide information on an individual’s genetic predisposition to certain medical diseases or conditions, which may help to make decisions about lifestyle choices or to inform discussions with a health care professional.
The FDA reviewed data for the 23andMe GHR tests through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device. Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the tests’ accuracy, reliability and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar GHR tests.
In addition, the FDA intends to exempt additional 23andMe GHR tests from the FDA’s premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible and in the least burdensome way, after a one-time FDA review.
The FDA requires the results of all DTC tests used for medical purposes be communicated in a way that consumers can understand and use. A user study showed that the 23andMe GHR tests’ instructions and reports were easy to follow and understand. The study indicated that people using the tests understood more than 90 percent of the information presented in the reports.

The Federal Trade Commission has published consumer protection materials relevant to purchasing DTC testing products. 23andMe has had a number of regulatory encounters with the FDA over the last several years (see earlier post here), and is slowly achieving more official recognition of their health-related testing products. However, the DTC dimension of these products is still a source of professional concern and caution among genetics professionals (see here). Market reception for these products will indicate whether a cohort of consumers develops which can be studied for their use and satisfaction with these testing services.

August 31, 2016

Will the 2016 Presidential Candidates Debate Science and Technology Policy?

In an effort to import more scientifically-based policy issues into the 2016 election, ScienceDebate.org, a coalition of science-based and academic organizations, has issued a challenge to the Presidential candidates regarding their views on policies impacting the science sector (broadly construed). ScienceDebate.org is calling for a Presidential debate focused on science and technology issues, with an online petition in support of such an event posted on their site. This effort was also conducted in earlier Presidential elections (see 2012 initiative); to date, there have been no such debates. The official Presidential debates are managed by a somewhat ad hoc organization, the Commission on Presidential Debates. The official debates this election cycle do not have subject matter limits. ScienceDebate.org has also posted a list of 20 questions, culled from submissions by the participating organizations, for the candidates (Clinton, Trump, Johnson, Stein), who are invited to submit answers. There are foundational questions that impact the science sector generally, related to innovation, research funding, education, immigration and regulations. The most prominent life science-related questions are the following: 
Biodiversity: Biological diversity provides food, fiber, medicines, clean water and many other products and services on which we depend every day. Scientists are finding that the variety and variability of life is diminishing at an alarming rate as a result of human activity. What steps will you take to protect biological diversity?
Food: Agriculture involves a complex balance of land and energy use, worker health and safety, water use and quality, and access to healthy and affordable food, all of which have inputs of objective knowledge from science. How would you manage the U.S. agricultural enterprise to our highest benefit in the most sustainable way?
Public Health: Public health efforts like smoking cessation, drunk driving laws, vaccination, and water fluoridation have improved health and productivity and save millions of lives. How would you improve federal research and our public health system to better protect Americans from emerging diseases and other public health threats, such as antibiotic resistant superbugs?
Vaccinations: Public health officials warn that we need to take more steps to prevent international epidemics from viruses such as Ebola and Zika. Meanwhile, measles is resurgent due to decreasing vaccination rates. How will your administration support vaccine science?
There are several questions related to mental health issues, and the epidemic of opioid abuse. The rest of the list poses specific questions related to energy, environment, space, and the Internet. 

It is likely that the campaigns will respond to the written questions. Probably the most conspicuous omission (relative to the volume of recent debate and controversy in the life science community) is the emerging issue of the management and uses of gene-editing technologies (see earlier posts here and here). Additionally, there is no explicit acknowledgment of dual-use research in the life sciences (see earlier posts here and here). Nonetheless, the organization does elevate the visibility of science-related policies as central aspects of 21st century governance, and implicitly suggests that any credible candidate in 2016 needs to exhibit some degree of scientific literacy.

July 23, 2016

Congressional Impasse on Zika Virus Funding Impacts Public Health Efforts in Peak Summer Months

The Zika virus outbreak is spreading in the U.S., according to local public health authorities and the federal Centers for Disease Control (CDC); international Zika virus cases are also increasing. Infection occurs because of a mosquito bite that transmits the virus, and most public health interventions to date concentrate on limiting exposure to the mosquito (Aedes aegypti). As of yet, there is no vaccine or specific treatment for the Zika virus. The discovery that Zika virus infection in pregnant women can lead to birth defects, including microcephaly, raised the alarm about the spread of the virus in this population (see earlier post here). To date, there are about 1400 reported cases in the U.S; there are about 400 cases of Zika infection in pregnant women. Most cases in the U.S. are traced to individuals traveling outside the country, returning with the infection; Puerto Rico, Brazil and other Caribbean and Latin American countries are some of the hotspots of transmission. Now, however, there  appear to be are several cases of local transmission of the Zika virus in Florida, which means that the virus is gaining a foothold in the U.S. itself. As in most public health crises, the government is tasked with providing increased support to local authorities, funding for treatment developments, and other activities. Congress has been in a stalemate over emergency Zika virus funding over the last month. President Obama sought $1.9 billion in new dedicated funding; the House of Representatives approved $1.1 billion. On to the Senate, where several provisions inserted into the funding bill encountered opposition; most notably, an explicit ban on Planned Parenthood as the recipient of any new funds. As discussed in an earlier post, because of the risk that Zika virus infection poses to pregnant women, who are at risk to give birth to babies with developmental disorders (and not all are known at this point), access to contraception and other reproductive services would appear to be a key ingredient in minimizing the birth of Zika-affected babies. That’s where the usual political conflict over reproductive and family planning funding entered the Zika funding legislation, and created an impasse. So to date, the Senate has not approved the funding that the House approved, and Congress has taken its usual lengthy summer break without acting on emergency funding for Zika virus research and support. The 7-week hiatus in the Zika funding battle has dismayed federal public health officials. The American Medical Association  (AMA) faulted Congress
At a time when concerns continue to mount about the nation's readiness to protect the public from the Zika virus, the AMA is disappointed by Congress' failure to pass legislation before adjourning for summer recess that would provide the resources necessary for our country to respond to this looming public health crisis. Without ensuring there are sufficient resources available for research, prevention, control and treatment of illnesses associated with the Zika virus, the United States will be ill-equipped to deploy the kind of public health response needed to keep our citizens safe and healthy—especially since the spread of mosquito-borne illness is accelerated during the summer months.
Editorials in some of the hardest hit areas of the country noted how the impasse would adversely affect their regions; here is the Palm Beach Post from Florida on the local impact: 
Congress has left the building. And in its dysfunctional wake, it leaves yet another failed effort at passing crucial emergency funding to fight the spread of the dreaded Zika virus. For at least the next seven weeks, Florida — which has distinguished itself as ground zero for cases of the mosquito-borne virus — will just have to hope that the worst part of the rainy storm season doesn’t translate into more infections. (Palm Beach County has seen about 12 cases of travel-related Zika.) It may be a long, hot summer. Mosquitoes that carry the Zika virus breed year-round here, and the number of infections in the continental United States is mounting. On Monday, the state Health Department reported 13 new cases of the Zika virus in Florida - the most reported cases of the virus in a single day. Moreover, federal officials say they will have to postpone a slew of anti-Zika actions. For example, the U.S. Centers for Disease Control and Prevention will have “limited capacity” to help with efforts to counter mosquito populations in the continental U.S. and territories. 
Yes, it should be noted that the CDC is now dispersing about 60 million dollars currently to localities to augment public health efforts, but these are “stopgap” awards that will not approach the scale of the demand. Congress returns on September 6th.

July 17, 2016

Congress Passes Federal Labeling Requirement for Genetically Engineered Foods; State Labeling Laws Would Be Preempted

Vermont enacted the first state law that requires the manufacturers of food products with genetically engineered (GE) ingredients to label their food products accordingly. Its Act 120 became law on July 1, 2016. However, for decades, there has been an ongoing battle at the federal level over whether a national labeling scheme should be enacted (the term GMO/genetically modified organism is also used). (See earlier posts for more background). So, after the Vermont bill became effective, there was a flurry of activity in Congress again to address the issue of a federal labeling scheme for GE food products. (The FDA has not required labels on food products with GE ingredients, in a policy that dates back to 1992). The Senate recently passed a bill, S. 764, that would mandate a particular federal labeling scheme for GE ingredients, and would also preempt any state labeling laws. The federal bill uses the term "bioengineering" to describe the products covered by the law: 
[F]ood - (A) that contains genetic material that has been modified through in vitro recombinant [DNA] techniques; and (B) for which the modification could not otherwise be obtained through conventional breeding or found in nature. 
There is an explicit statement of the preemption achieved by this legislation: 
No State or a political subdivision of a State may directly or indirectly establish under any authority or continue in effect as to any food or seed in interstate commerce any requirement relating to the labeling of whether a food (including food served in a restaurant or similar establishment) or seed is genetically engineered (which  shall  include such other similar terms as determined by the Secretary of Agriculture) or was developed or produced using genetic engineering, including any requirement for claims that a food or seed is or contains an ingredient that was developed or produced using genetic engineering.
This last provision is aimed at the recent Vermont law, as well as other initiatives in Connecticut, Maine and Alaska. Since its enactment in 2014, the Vermont law had already impacted the food and restaurant industries, with some major players declaring that they would provide labels in anticipation of the law (see here). It was apparent that the Vermont law had immediate national impact, as food manufacturers faced compliance with the statute or avoidance of Vermont’s market (practically unworkable). Now, the House of Representatives has passed a version of the recent Senate bill, and it goes to President Obama for signing; it appears that he will sign it. The clear effect of the federal bill is to preempt the long-sought state labeling laws. However, does this bill actually require a label? The bill departs from other labeling proposals over the years (state and federal) in that it contains no explicit requirement to provide a “GMO” or other GE-related name on the main label of the product. The actual labeling scheme in the new federal law is quite elastic, describing the format of the labeling as follows: 
[T]he form of a food disclosure under this section be a text, symbol, or electronic or digital link. 
Thus, a consumer could use a smartphone to read a QR code, or utilize a provided link to access information, or read whatever disclosure material the manufacturer has chosen to provide. The forms of the notification could be arguably obscure, and indirect. In other words, at least so far, there will be no uniformity of disclosure. Already, there are allegations that the bill is discriminatory in that it will make it harder for some consumers to pursue the informational references; access to digitally formatted information is not universal. The USDA has two years to make the law operational, and may refine the labeling formats in that period, subject to public input.