Individuals living with sickle cell disease, a hereditary blood disorder that can cause great
pain and premature death, until about a decade ago had few treatment options and even fewer
hopes of finding a cure. That all changed in 2012 with the discovery of CRISPR-Cas9, a tool
found naturally in bacteria that can be used to edit the DNA of living cells [1]. The system is
composed of three parts: CRISPR (clustered regularly interspaced short palindromic repeats)
RNA combines with a CRISPR-associated nuclease (Cas) and a specially designed guide RNA
to act as a pair of “molecular scissors”, enabling researchers to selectively target specific
segments of DNA in cells and edit them. Sickle cell was immediately identified as a potential
therapeutic target due to a single point mutation in a patient’s genome causing the disease. The
first sickle cell patient to be treated with CRISPR-Cas9 was 34 year old Victoria Gray, who
received an infusion of 2 billion of her own edited red blood cells in 2019, and has since been
living pain free without the need for any more intervention [2]. Her treatment, under the name
CASGEVYTM, was developed jointly by Vertex Pharmaceuticals and CRISPR Therapeutics, and
has been approved by the FDA. While nearly ready to be available on the market, there is one
major obstacle standing in between patients and the treatment: an intensive legal battle
surrounding the intellectual property of the CRISPR system.
Associated with the ground-breaking development of CRISPR are the winners of the
2020 Nobel Prize in Chemistry, Jennifer Doudna and Emannuelle Charpentier. Doudna, a
researcher and professor at UC Berkeley, and Charpentier, of the Max Planck Institute in Berlin,
jointly published their first paper describing the CRISPR system in the August 2012 edition of
Science. That same year they filed a patent, the first steps in commercializing their discovery
through the booming field of biotechnology. However, another young researcher, Feng Zhang of
Harvard, along with his mentor George Church, were working on the development of CRISPR at
the same time. Having filed for a patent in November of 2012, they published their own paper in
January of 2013 [3]. While Zhang and Doudna began as collaborators, they quickly turned into
competitors after Zhang’s patent was granted first, despite being filed later, as he had paid $70 to
have his application fast-tracked [4]. Doudna discredited Zhang’s contributions to early CRISPR
research, and stated that she and Charpentier had gotten there first. The subtle difference in
credibility is that Doudna uncovered the structure and basic function of CRISPR-Cas9, but
Zhang is credited with discovering how to get CRISPR into human cells to edit DNA [5].
Doudna’s patent was also granted later, which meant both scientists had patented essentially the
same system, raising many legal issues in the commercialization of CRISPR-Cas9.
The issue at hand is exemplified with the case of CASGEVYTM as a treatment for sickle
cell disease. Doudna was a founding member of CRISPR Therapeutics in 2013, which later
worked with Vertex to develop CASGEVYTM. Zhang, initially in collaboration with Doudna,
founded another company, Editas Medicine that same year. Doudna ultimately decided to leave
only 7 months later, feeling like she was being pushed out by the other co-founders [6]. Today,
Editas Medicine, with its own sickle cell treatment in the discovery pipeline, has every reason to
view Vertex as a competitor. As MIT journalist Antonio Regalado put it, “Editas will want
Vertex to pay.” If they refuse, the company’s lawyers could go as far as to “try and get an
injunction to stop the treatment from being sold” [7]. This potential lawsuit could drag out the
deployment of the life-saving treatment to the market as lawyers argue over intellectual property,
infringement, and licensing.
Vertex, it seems, does not want to face a lengthy court battle, at least not yet. In late 2023,
they reached a tentative deal with Zhang and Editas to license the CRISPR-Cas9 technology for
100 million dollars, to be paid in installments [8]. This may seem to be an acceptable
compromise; however, for a treatment that already costs 2.2 million dollars per dose [9], the
extra expense of the licensing agreement will surely be passed on to those who need the
treatment and their insurers. The legal battle is ongoing, as Charpentier, Doudna’s longtime
collaborator and co-founder of CRISPR therapeutics, appealed the decision that granted Zhang
the exclusive right to CRISPR-Cas9 in 2022 [10]. The lawsuit is still ongoing, but if she is
successful, the licensing deal between Vertex and Editas will likely not be upheld, and Vertex
will be free to sell their product at last.
There has been extensive debate over the ethics of patenting biological processes and
prenatal treatments ever since the dawn of the biotechnology field. In 2013, the US Supreme
Court decided that naturally occurring elements of biology, such as a gene, are unpatentable [11].
However, modifications to natural elements, such as genetically modified organisms (GMOs),
are covered under patent law. CRISPR technology falls into the latter category; while it was
derived from a natural process in bacteria, the customization required to treat human disease
using the system qualifies as an “inventive step” necessary for a patent. The main concerns over
the use of patents in biotechnology involve the commercialization and commodification of the
human body, and the prevention of affordable access to the products by those who need them
[12]. On the other hand, patents are necessary to incite innovation in a capitalistic economy: if
there is no financial payoff after investing millions into developing a treatment, why would
anyone do it? This requires a delicate balance. Scientists and biotechnology companies should be
able to profit from their hard work and discoveries, while at the same time products and services
must be affordable and available to the people who need them. Much work has to be done in the
field of patent law to achieve this goal, making a fair system for CRISPR developers and
beneficiaries.
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