April 27, 2017

March on Science Movement Focuses on Trump-Era Science Policies

The March for Science on April 22, 2017 focused national attention on a number of science-impacting developments under the Trump administration. The march heralds more of developing movement than a single event. For the biomedical research community, the immediate concern is a proposed cut to the National Institutes of Health (NIH) budget of about 18% which is quite radical, and is a sharp departure from the recent Congressional efforts to restore the NIH funding decline over the last decade (see factsheet). A commentary by Harold Varmus, Nobel Prize winner and former director of NIH, notes the national effects of reductions to the NIH budget:
To understand just how devastating a cut of less than 20 percent of an agency’s budget would be requires some understanding of how the N.I.H. operates. Very little of its typical annual budget is spent on the agency’s administration: The industrious, underpaid government scientists who manage the funding of the N.I.H.’s research programs consume less than 5 percent of its budget. Only a bit more, about 10 percent, supports the work of government scientists. In sharp contrast, over 80 percent of its resources are devoted to competitively reviewed biomedical research projects, training programs and science centers, affecting nearly every district in the country.
Ironically, at the close of the Obama administration, Congress passed the 21st Century Cures Act, which would add a new $6 billion to medical research; it received widespread bipartisan support. It was particularly welcomed by the NIH leadership as promoting several new frontier initiatives: Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and the Precision Medicine Initiative (PMI). 

So the NIH funding climate remains turbulent, which is not optimal for a funding agency that makes multi-year grants to researchers. The NIH budget proposal was a motivating factor for many march participants, including research scientists. The disconnect between the vitality of American biomedical science and the political vulnerability of federal support is readily apparent. Decades of investment in life science research has had a cumulative effect of integrating molecular biology into medical practice, with many prospects for precise and targeted interventions in disease processes. But it's more than that at stake; the generation of scientific knowledge as a public good is an enterprise worth funding and protecting.

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.