December 21, 2015

Federal Circuit Denial of Rehearing for Prenatal DNA Testing Patent: Supreme Court Review?

The Federal Circuit denied a petition for an en banc rehearing of Ariosa v. Sequenom (Fed. Cir 2015). This case tests the patent eligibility of a method to detect fetal DNA in maternal blood in order to perform prenatal testing. This case is set against a lingering unrest over the recent Supreme Court decision in Mayo v. Prometheus (2012), invalidating a method of drug dosaging as the improper patenting of a natural phenomenon. Claim 1 of the Sequenom patent is as follows: 
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. 
The denial was accompanied by two concurring opinions (Judges Lourie and Moore, Judge Dyk) and one dissent (Judge Newman). The concurrences both thought that Ariosa was wrongly decided as a policy matter, but that their court was bound by the Mayo decision. In Mayo, a 2-part test which required the identification of any "patent-ineligible concept" and if found, a patent claim would then need an "inventive concept" to make the claim patentable.

Application of the Mayo test in the panel decision of the Federal Circuit identified a natural phenomenon (the presence of the fetal DNA in maternal serum) in Claim 1 that was appended to conventional laboratory techniques (not to an inventive concept) and that result did not present a patentable invention. The recent petition for a rehearing and the accompanying amici involvement indicate continued discomfort with Mayo’s demand for the addition of an inventive concept to any discovered natural phenomeon before patenting is permitted. An “inventive concept” is not identified, nor is that requirement demanded by the statute or even explicitly required by the earlier 35 U.S.C. 101 landmark cases of the high Court (while also suggesting a consideration of prior art as well). It should be noted that the current debate is particularly centered on method claims, especially those with either diagnostic or therapeutic application. Will the Mayo test not only invalidate many diagnostic patent claims but challenge the eligibility of standard pharmaceutical treatment claims, for example, if the underlying metabolic processes are simply natural phenomena? Judge Dyk suggested that the Mayo framework may overlook a form of creativity that can emerge from discovery-based effort: 

But, as I see it, there is a problem with Mayo insofar as it concludes  that  inventive concept cannot come from  discovering something new in nature — e.g. , identification  of a previously  unknown natural relationship or property. In my view, Mayo did not fully take into account the fact that an inventive concept can come not just from creative and unconventional application of a natural law, but also from the creativity and novelty of the discovery of the law itself. This is especially true in the life sciences, where development of useful new diagnostic and therapeutic methods is driven by investigation of complex biological systems.
Thus, until the Supreme Court returns to consider whether Mayo has imposed a rigid, inflexible test with inapposite and/or ambiguous requirements, many argue that diagnostic and therapeutic innovation is at risk. Alternatively, however, more attention to embedding unambiguously detailed and physical manipulation into patent claims may overcome some of the concerns with breadth and scope underlying the preemption rationale for exclusion of the type of claim seen in the Sequenom patent. A petition for certiorari to the Supreme Court can be expected; 2016 could see the Court return to the issue of life science patent eligibility.

December 3, 2015

International Summit on Human Gene Editing: No Recommendation for Ban or Moratorium on Germline Gene Editing Research

The International Summit on Human Gene Editing, hosted by the National Academies of Science and Medicine (NAS, NAM) and international partners, has just concluded a 3-day meeting (archived webcast available here). This summit was called following the rapid dissemination of human gene editing research using the CRISPR/Cas 9 technology (see earlier posts here and here). The impact of this technology cannot be understated: 
The rapid development and widespread adoption of easy-to-use, inexpensive and effective genome-editing methodologies has changed the landscape of biology. The simplicity of the CRISPR–Cas9 system allows researchers and students to make precise changes to genomes, thereby enabling many experiments that were previously difficult or impossible to conduct.
Widespread concern over possible attempts to engineer the human germline (perform gene editing on embryos or gametes for reproductive purposes) led to calls for caution or even a research moratorium (see here). At the conference this week, panels discussed the current technical state of human gene editing, existing and potential governance structures, international perspectives, and social consequences of the technology. The most controversial application of human gene editing – germline editing creating heritable genetic changes – was central to many of the discussions, and the conference oscillated between considering the legitimacy of germline editing and considering the arguably more mundane regulatory control of somatic gene editing. The conference coordinating committee has released a consensus statement that endorses further research on both somatic and germ-line gene editing, subject to existing regulations and oversight mechanisms. The full statement is here. I reproduce the portion of that statement that focuses on the hotly contested issue of germline gene editing:
3. Clinical Use: Germline. Gene editing might also be used, in principle, to make genetic alterations in gametes or embryos, which will be carried by all of the cells of a resulting child and will be passed on to subsequent generations as part of the human gene pool. Examples that have been proposed range from avoidance of severe inherited diseases to ‘enhancement’ of human capabilities. Such modifications of human genomes might include the introduction of naturally occurring variants or totally novel genetic changes thought to be beneficial.

Germline editing poses many important issues, including: (i) the risks of inaccurate editing (such as off-target mutations) and incomplete editing of the cells of early-stage embryos (mosaicism); (ii) the difficulty of predicting harmful effects that genetic changes may have under the wide range of circumstances experienced by the human population, including interactions with other genetic variants and with the environment; (iii) the obligation to consider implications for both the individual and the future generations who will carry the genetic alterations; (iv) the fact that, once introduced into the human population, genetic alterations would be difficult to remove and would not remain within any single community or country; (v) the possibility that permanent genetic ‘enhancements’ to subsets of the population could exacerbate social inequities or be used coercively; and (vi) the moral and ethical considerations in purposefully altering human evolution using this technology.

It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application. Moreover, any clinical use should proceed only under appropriate regulatory oversight. At present, these criteria have not been met for any proposed clinical use: the safety issues have not yet been adequately explored; the cases of most compelling benefit are limited; and many nations have legislative or regulatory bans on germline modification. However, as scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis.
 As reported by David Baltimore, chair of the conference committee, the members did not recommend either a ban or a moratorium on research into germline gene editing, but they state that any use of gene editing in reproduction at this time would be "irresponsible."  In the U.S., the NIH has already ruled out federal funding for such research:
However, NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. 
The NAS contemplates ongoing public engagement with the controversies raised by human gene editing, in the form of an upcoming formal NAS study and the establishment of a publicly accessible forum to continue the discussion. More analysis of the conference and the effects on the current research climate will be posted here.