A Primer on the CRISPR Patent Battle

Posted By Jey Kumarasamy

Meet CRISPR, a revolutionary gene editing tool of “unprecedented precision, efficiency and flexibility”. MIT Technology Review has called it “the biggest biotech discovery of the century.” And its scientific and commercial potential has made it “one of the hottest investments” in the biotechnology industry.

CRISPR is based on a naturally-occurring, defense mechanism found in a wide range of bacteria to combat virus DNA. It uses the protein Cas9 and a “tailored guide RNA sequence to cut and splice material from or into the DNA helix.” Potential areas of application include agriculture, industrial biotechnology and, of course, the treatment of human diseases.

No one disputes that CRISPR is a groundbreaking invention. Instead, the most salient issue is regarding who owns the patent rights to the technology. Two research teams are currently involved in a high-stakes patent dispute in the US. On one side, there is Jennifer Doudna and her team at the University of California, Berkeley. On the other, there is Feng Zhang and his team at the Broad Institute, a Massachusetts-based research centre partnered with the Massachusetts Institute of Technology and Harvard University. Both scientists claim to have invented CRISPR first.

Doudna & Zhang
Jennifer Doudna (left) and Feng Zhang (right) are the two leading scientists involved in the US patent dispute over CRISPR (Source: STAT)

First-to-invent versus first-to-file system

Before getting into the details of this particular legal dispute, there is some important background information we need to understand.

Until very recently, the US was the last country in the world to employ a first-to-invent system rather than a first-to-file system. In a first-to-invent system, the patent to an invention disputed by two parties would be given to the one who could prove that they were the first to invent it. This was accomplished through a process called “interference proceedings”.

On March 16, 2013, the US switched to a first-to-file system where priority is given to the first inventor to file a patent application, thereby eliminating the need for interference proceedings. This change was part of the America Invents Act.

Patent applications

The chronology of events is critical to this dispute.

The Berkeley team was first to initiate their patent application for the CRISPR technology in May 2012. The Broad team followed with their own provisional patent application in December 2012. Under the current first-to-file system, the story would likely end here. But since both these applications have a priority date earlier than March 16, 2013, they fall under the older first-to-invent regime.

The Broad team, unlike the Berkeley team, had requested that its application be expedited under the USPTO Track One program. Therefore, they were granted the patent in April 2014 before the Berkeley team’s application had even been reviewed. Another difference was that the Broad application specifically considered application of the technology in eukaryotic cells, which tend to be found in more complex organisms (e.g. humans), as opposed to prokaryotic cells that have a simpler structure (e.g. bacterial cells). While their patent application was being reviewed, Zhang submitted a personal declaration arguing that it was not obvious from the Berkeley team’s earlier filings that the technique could also be applied in eukaryotic cells.

In April 2015, the Berkeley team amended their application to include both eukaryotic and prokaryotic cells. They also requested for a patent interference by filing a “Suggestion of Interference” against several Broad patents, including the one mentioned above. The USPTO granted their request in January 2016.

Interference proceeding

Patent interference proceedings are considered to be highly technical. Ultimately, a panel of three USPTO patent judges will decide which team gets patent rights to the technology. Each party may submit evidence, in writing or in the form of oral arguments, to establish that they invented the CRISPR application to gene editing first. Oral hearings have been scheduled for November 17, 2016.

In addition, the panel determined the Berkeley team to be the “senior party” and the Broad team to be the “junior party” based on the filing dates. In interference proceedings, the burden of proof lies on the junior party. Therefore, the Broad team will need to convince the panel that the patent office was correct to grant them their CRISPR patents.

It seems that it may take a couple years before a decision is finally rendered. Even then, many expect that the losing party will appeal the decision because of the “high financial stakes.”

Furthermore, this may be a sneak peek of what is to come in other jurisdictions around the world. In Europe, for instance, the Broad team “fast-tracked several of its applications at the European Patent Office (EPO), and has been awarded several patents so far.” The Berkeley team has also filed a patent application but it is still pending. Last year, nine parties came forward to launch an opposition procedure against the first European CRISPR patent awarded to the Broad team. This dispute may also take years before it is resolved.

Conclusion

It will probably be quite a while before we know how this story ends. As mentioned, CRISPR has been described by some as the “the biggest biotech discovery of the century.” This alone suggests that there is sufficient financial incentive for the players involved to slog through this patent battle.

Meanwhile, the uncertainty over who owns the patent rights to this technology does not seem to have slowed down investment in CRISPR-related research and development. A few months ago, Editas Medicine, a Massachusetts-based biotechnology firm co-founded by Zhang, raised US$94 million on its IPO. Other biotechnology firms that are seeking to use the CRIPSR technology to develop successful human therapeutics include Crispr Therapeutics and Caribou Biosciences (co-founded by Doudna).

As for why the scientific community does not seem to be waiting for the legal dispute to be resolved first, Robin Feldman, a professor at the UC Hastings Law School, sums it up quite well: “The patent system lumbers on. But innovation is on its own timeline.”

CRISPR technology
A summary of how the CRISPR technology is used to edit a gene (Source: Business Insider)

Personal Health Data Breaches in Hopkins v Kay, 2015 ONCA 112

Posted By Jey Kumarasamy

Overview

The Ontario Court of Appeal’s decision in Hopkins v Kay involved a proposed class action proceeding against a hospital for the unauthorized access of personal health information by its employees.

The health information of the respondent, Erkenraadje Wensvoort, was improperly accessed by employees at the Peterborough Regional Health Centre (“hospital”). She was one of the 280 patients who were notified by the hospital, as required by Ontario’s Personal Health Information Protection Act (“PHIPA”), that the privacy of their personal health information had been breached. The respondent feared that her ex-husband, who had hurt her in the past, had orchestrated the breach in an attempt to locate her.

As a result, the respondent brought forward a common law claim for intrusion upon seclusion against the hospital and some of its employees.

The appellants sought to have the action dismissed on the grounds that PHIPA is an exhaustive code, which precludes the Superior Court from entertaining any causes of actions external to it, including those found in the common law.

The motion judge dismissed the appellants’ motion and allowed the respondent to bring her claim in the Superior Court.

The issue on appeal was whether the respondent is precluded from bringing a common law claim for intrusion upon seclusion in the Superior Court on the basis that PHIPA creates an exhaustive code. The Information and Privacy Commissioner of Ontario (“Commissioner”), who is responsible for the administration and enforcement of PHIPA, intervened in support of the respondent’s position.

Court of Appeal’s decision

The Court of Appeal concluded that PHIPA does not preclude a common law claim for intrusion upon seclusion. Their analysis centered on whether there was a legislative intention to create an exhaustive code with regards to PHIPA.

As there was no such explicit intention stated in PHIPA, the Court turned to the three factors listed by Cromwell J.A. in Pleau v Canada that should be considered when determining whether the legislature intended to create an exhaustive code.

First, the Court assessed whether “the process for dispute resolution” established in PHIPA is consistent with exclusive jurisdiction. To this extent, the Court recognized that the Act contains a “comprehensive set of rules about the manner in which personal health information may be collected, used, or disclosed across Ontario’s health care system.” However, the sections regarding the resolution of disputes give much discretion to the Commissioner, and the language (e.g. s. 57(4)(b) and s. 71) specifically contemplates the possibility that certain complaints related to personal health information may be the subject of a procedure that falls outside the scope of PHIPA.

Second, the Court looked at the “essential character” of the claim and asked whether the court’s assumption of jurisdiction would be consistent with the PHIPA scheme. The respondent’s claim for intrusion upon seclusion was based on the common law tort recognized in Jones v Tsige, and does not depend on PHIPA. The Court did not accept the appellants’ argument that allowing the respondent to pursue this cause of action would effectively amount to a circumvention of the statutory restrictions and limitations contained in PHIPA. Instead, the Court held that the respondent’s burden was higher now as a result of the additional elements required by a Jones v Tsige claim. The Court did acknowledge, however, that proof of actual harm is not required under the common law claim, unlike under PHIPA. Additionally, the alleged difference in the limitation periods of the two causes of actions was held to be insignificant in practice.

Finally, the Court assessed the Act’s capacity to afford “effective redress”. The Court once again highlighted the informal and discretionary nature of the review procedure under PHIPA, especially the Commissioner’s prerogative, pursuant to s. 57(4), to not review a complaint for any reason he or she considers appropriate. At this stage, the Court gave significant weight to the Commissioner’s own submission that “granting him exclusive jurisdiction over individual claims would impair his ability to focus on broader issues.” This, along with the Court’s own determination that the review procedure reflects a statutory focus on systemic issues, led the Court to postulate that it is plausible that many complaints of merit would never result in an order from the Commissioner.

Thus, the Court concluded that there was no legislative intention to create an exhaustive code and confer exclusive jurisdiction on the Commissioner.

Conclusion

The frequency and severity of personal health data breaches seem to be following a dangerous trend in Canada. The privacy commissioners of both British Columbia and Alberta have recently reported that health workers “snooping” on private data is among the most common breaches, and that “improper access of health information is becoming an epidemic.” In this context, the Court’s decision in Hopkins v Kay is a significant one. Allowing civil actions to be commenced outside the regime established by PHIPA for breach of personal health information in Ontario increases the legal options available to plaintiffs and potentially increases the legal risk for health information custodians.

How We Talk About Medicine: Pushing the Boundaries

Posted By Jey Kumarasamy

In health or medicine-related articles, there are two prevalent sets of labels imposed on medicinal products. On the one hand, there are labels like “Western”, “mainstream”, and “conventional” medicine. On the other hand, there are terms such as “traditional”, “alternative”, and “complementary” medicine. These designations are commonly used in the media, medical literature, and sometimes, even in legal decisions.

The “Western medicine” label reflects its historical origin, but is now commonly practiced and studied around the world. It is also usually associated with biomedicine and scientific findings. As for “traditional medicine”, the World Health Organization provides the following definition:

“Traditional medicine is the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness.”

False Dichotomy

These labels are sometimes used to suggest that the two categories are mutually exclusive. For instance, it could be construed that no part of traditional medicine has any scientific basis, or that Western medicine does not encompass any traditional treatments. However, these propositions are difficult to uphold in the presence of clear counterexamples like the “CIHR Team in Aboriginal Antidiabetic Medicines” project. This Quebec-based multidisciplinary endeavor explores “the antidiabetic potential of Cree Traditional Medicine (TM) involving Boreal forest plants.” It is funded by the Canadian Institutes of Health Research, includes members of various Cree health institutions, and has produced several scientific publications. Perhaps this false dichotomy – of “Western” vs. “traditional” medicine – would be less significant were it limited to such fora as blogs and social media. Unfortunately, that is not the case.

A quick CanLII search for Canadian cases in the last 10 years containing the phrase “Western medicine” returns 48 results. Two of these results are the controversial case of Hamilton Health Sciences Corp. v D.H. and its clarification that followed in 2015. They were discussed in a recent MJLH blog post written by my colleague, Lauren Hanon.

Hamilton Health Sciences Corp. v D.H.

In the initial judgement, Justice Gethin Edward held that the McMaster Children’s Hospital in Hamilton cannot force an 11-year-old First Nations girl diagnosed with high-risk acute lymphoblastic leukemia to resume chemotherapy against her mother’s wishes. The girl, identified as J.J., was removed midway from her 32-day chemotherapy treatment plan by her mother, D.H., who wanted to pursue traditional medicine instead. Justice Edward upheld D.H.’s right to do so under section 35 of the Constitution Act, 1982, which recognizes existing aboriginal and treaty rights. Seven months later, after the cancer, which had been in remission, returned and the parties submitted a joint submission to the court, Justice Edward delivered a clarification. He reaffirmed that “the best interests of the child remain paramount.”

The judgment sparked quite a controversy in the media. It diverged from previous cases where courts have forced medical treatment on non-aboriginal minors considered not capable of making their own decisions. One such example is the Supreme Court of Canada’s judgement in A.C. v Manitoba (Director of Child and Family Services) in 2009, in which the court found that a forced blood transfusion, despite the 14-year-old Jehovah’s Witness girl’s objections, was constitutionally sound. However, Justice Edward notes at the end of his judgment on J.J.’s case that section 35, the source of D.H.’s right to pursue traditional medicine, is not contained within the Canadian Charter of Rights and Freedoms, and therefore falls outside the scope of section 1 – the Charter’s reasonable limits clause.

There is an interesting passage in Justice Edward’s original judgement, which brings us back to the discussion of labels:

“D.H.’s decision to pursue traditional medicine for her daughter, J.J., is her aboriginal right. Further, such a right cannot be qualified as a right only if it is proven to work by employing the Western medical paradigm.” [emphasis added]

Even though this passage references the aboriginal right itself and does not comment on the effectiveness of any treatment, the phrase “Western medical paradigm” seems to reduce chemotherapy and the medical opinion of the doctors at McMaster Children’s Hospital to a matter of culture. To be clear, this is not to say that Western medicine is more effective than traditional medicine, or vice versa. Rather, language like this is distracting and confusing, especially if we also have to consider questions like which treatment is simply more likely to be effective. Proponents for labels like “biomedicine”, “evidence-based medicine” or “science-based medicine” have raised similar arguments.

In the case of J.J., her mother originally chose treatment at the Hippocrates Health Institute (“HHI”) over the chemotherapy treatment provided at the Hamilton hospital. HHI advertises itself online as a centre for alternative medicine, and its director claims that they have “had more people reverse cancer than any institute in the history of health care.” HHI is licensed in Florida as a “massage establishment”, and it is being sued by former employees who allege that they were wrongfully dismissed after raising concerns about “ethical transgressions in regard to the medical treatment of patients at the facility.”

HHI was also the destination of another 11-year-old Ontario First Nations girl, Makayla Sault, after she left chemotherapy at McMaster Children’s Hospital for the same type of cancer in 2014. Makayla Sault unfortunately died several months later after she relapsed, following a period of remission.

The “Comprehensive Cancer Wellness Program” page on HHI’s current website has the following disclaimer at the bottom of the page (earlier snapshots on the WayBackMachine archive seem to indicate that the contents of the website were different last year):

“DISCLAIMER: This program is an advanced educational process, and is not intended to diagnose, treat, prevent, or cure any disease and is not a replacement for standard medical care. For any concerns or questions you should always seek advice from your primary care provider.”

Meanwhile, the doctors at McMaster Children’s Hospital insisted that J.J. had at least a 90% chance of being cured if treated with chemotherapy. And after J.J.’s cancer returned, her family decided to resume chemotherapy along with aboriginal medicine. The health-care team responsible for her now includes “a senior pediatric oncologist and a Haudenosaunee (Iroquois) chief with experience in native medicine.” There have been no further reports regarding J.J.’s prognosis.

Conclusion

Justice Edward referred to HHI as an “alternative cancer treatment facility” – a generous characterization considering that even HHI does not intend its program to be an alternative treatment for any disease, and states this clearly in the disclaimer. Furthermore, the original judgment did not examine HHI, or compare the effectiveness of each of the proposed treatments. Perhaps it should have, because if the paramountcy of the best interests of the child was implicit, as suggested in the clarification, then this was likely a relevant component to the analysis. Resorting to labels like “Western” and “traditional” medicine, instead, only needlessly perpetuates the aforementioned false dichotomy. It is easy to get caught up in all these labels given their pervasiveness, and it is also possible that there is no perfect solution for the purpose of demarcation. But we must be cautious when drawing the dividing line in medicine, because if we choose to focus on the wrong set of distinguishing factors, we might miss the ones that make the difference between life and death.

Genetic Privacy and Bill S-201

Posted By Jey Kumarasamy

An individual’s genetic information can be used for diagnosing medical conditions, measuring the probability of developing or transmitting a genetic disorder, and personalizing treatment. Given the increase in genetic testing, the collection and use of genetic information continues to grow in prevalence.

Aside from the more apparent medical and research purposes, genetic information could also be used to make decisions related to insurance coverage or employment. Insurance underwriting requires the disclosure of relevant information in order for the insurer to properly assess risk.

The rise in genetic testing has prompted privacy concerns. Arguments for the right to a reasonable expectation of genetic privacy include the right not to have others know, and the right “not to know” about oneself. Proponents for allowing the use of genetic information by insurers argue that it is no different from other vital classification tools used for risk assessment, and that it allows for fair market prices.

Legal limitations

Legal responses to these concerns have varied. The US, in 2008, prohibited the use of genetic information for making employment or health insurance underwriting decisions. In Germany, genetic information may only be requested for life insurance policies that exceed a specified amount. Similarly, there is now a voluntary moratorium in the UK, set to expire in 2017, under which genetic information may only be used for life insurance policies over a specified limit (£500,000, or £300,000 for critical illness policies), and only if the genetic test and illness have been approved by an independent government committee.

At present, Canada lacks any similar federal prohibition or moratorium. The Canadian Life and Health Insurance Association (CLHIA) has stated that although an insurer would not require genetic testing, the insurer may request disclosure of genetic information from previously completed tests. This may soon change due to Bill S-201, An Act to prohibit and prevent genetic discrimination, which was introduced in October 2013. The Bill specifically addresses the use and disclosure of genetic information.

Bill S-201

Once in force, the Bill would prohibit anyone from requiring an individual to undergo a genetic test as a prerequisite to providing goods or services, or entering/continuing a contract (in whole or in part). Similarly, it would also prohibit requirements to disclose results from previous genetic tests. Under this Bill, therefore, employees or insurance underwriters would not be permitted to demand genetic information, save for one exception: an insurer may require the disclosure of genetic tests results for policies that exceed $1,000,000 or that pay a benefit of more than $75,000 per annum, if it is expressly permitted in an applicable provincial statute. Note that this still would not allow insurers to require new genetic tests – it would only apply to previous tests. Additionally, these prohibitions would not apply to medical professionals and researchers if it is for the purpose of medical care or research.

If convicted on indictment for contravening one of these prohibitions, one could face a fine of up to $1 million and/or imprisonment for a term not exceeding five years (or $300,000 and/or twelve months for a summary conviction).

The Bill also amends the Canada Labour Code and the Canadian Human Rights Act to expressly include genetic testing and genetic information.

Conclusion

As access to personal genetic information continues to improve, protection for genetic privacy proves to be a growing and pressing concern. While Bill S-201 would address many of the commonly raised issues regarding the use and disclosure of genetic information, it remains to be seen whether these provisions will become law, and if they provide the optimal solution.

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If you are interested in issues related to genetic privacy, be sure to attend our upcoming event, “Patenting Genetic Materials: Biotechnology and Intellectual Property Law

Neurolaw: The Potential and Pitfalls of a Newly Developing Field

Posted By Jey Kumarasamy

Neurolaw is an emerging field at the nexus of neuroscience and law. This blog post discusses the use of neuroscience in the legal system and its issues. The interest in neurolaw increased in the 1990s with advances in functional neuroimaging (e.g. fMRI). Functional neuroimaging measures neural activity in a specific region of the brain, which could then be used to explain one’s behaviour.

In 2000, a middle-aged male schoolteacher in Virginia was accused of collecting child pornography and trying to molest his stepdaughter. After complaining of headaches and a loss of balance, he underwent a brain scan. The MRI results revealed an egg-sized tumour pushing against the prefrontal lobe of his brain. This area of the brain controls judgment, impulse control and social behaviour. Once the tumour was removed, he stopped downloading child pornography and making unwanted sexual advances toward hospital staff. However, this lasted for only a year before he returned to his old behaviour. Another brain scan indicated that his tumour had returned. Once again, he started behaving normally after the tumour was removed. This is a rare case with a clear causal link between the neurological abnormality and criminal behaviour.

“My brain made me do it”

In Canada, there were 31 criminal cases that discussed electroencephalography (EEG) and 118 that discussed magnetic resonance imaging (MRI) between 2005 and 2010. In the US, the number of cases involving neuroscientific evidence doubled from 2006 to 2009.

In criminal law, one of the two essential elements for criminal liability is mens rea (i.e. the required mental element for the crime, often criminal intent).[1] With the development of the field of neurolaw, the defence in a criminal case can now put forward, for example, a neurological condition as an excuse from responsibility.

An early example of a criminal case in which the defence submitted neuroimaging evidence is R v Parks. The accused, Kenneth Parks, drove 23 kilometres to his in-laws’ house and attacked them with a kitchen knife and a blunt instrument, presumed to be a tire iron.[2] His mother-in-law died but his father-in-law survived. Parks then drove to a nearby police station and told the police that he thought he had killed both of them. The defence successfully argued that Parks could not be held responsible because his somnambulistic condition (i.e. sleepwalking) was legally classified as non-insane automatism. The evidence included an EEG report, which measured unusual activity in his brain. [3] The evidence satisfied the jury, and Parks was acquitted. In 1992, the Supreme Court of Canada upheld this decision.

Neuroscience also played a part in the landmark US Supreme Court case Roper v Simmons (2005) that found juvenile death penalties unconstitutional partly because of differences between juvenile and adult minds. The American Medical Association (AMA) and American Psychological Association (APA) each filed briefs citing studies that demonstrated “neurological, physiological, and psychological deficits” in the adolescent brain.

Potential applications

Although neurolaw has so far been used mostly by the defence in criminal cases, neurolaw may also be of some benefit to the prosecution. Application of neurolaw in Canada by the prosecution in criminal cases is quite possible in the future. It would also raise privacy issues, and necessarily shape privacy laws concerning an individual’s thoughts and memory. But it also highlights the pitfalls of neurolaw. For instance, a trial in India resulted in the conviction of a woman for the murder of her ex-fiancé. The decision was largely based on a brain scan using a new technology – Brain Electrical Oscillations Signature (BEOS). BEOS claims to be the next-generation lie detector. However, critics were alarmed that, at the time of the case, no peer-reviewed studies of BEOS had been published. The accused’s sentence was later suspended by the Bombay High Court, which made no mention of the BEOS evidence.

Advances in neuroscience may also have the potential to affect other aspects of the legal system. Procedures that might accurately measure one’s pain could revolutionize the way courts deal with personal injury (tort), workers’ compensation or insurance litigation. In the future, we could potentially use neuroimaging to confirm lack of bias in a prospective juror or as supporting evidence that the accused or a witness recognizes something.

Possible issues

As with any developing technology, many of the technologies commonly associated with neurolaw are not perfect and, in some instances, not reliable enough for use in court. Neurolaw usually relies on a correlation between brain activity in a specific region and a particular behaviour, but as the maxim states: correlation does not (necessarily) imply causation. In some cases, like the above-mentioned in which a man suddenly developed a sexual obsession with children, a causal link does seem evident; but such cases are the exception rather than the norm. Furthermore, brain scans are typically performed after the crime is committed. Can brain scans performed several weeks later ever accurately depict the mental state of the accused while committing the crime?

A recent study published in Science found that judges are more likely to list mental illness or psychopathy as a mitigating factor when sentencing an accused if there is evidence of a biomechanism underlying the psychopathy. The researchers presented the same psychiatric testimony as part of a hypothetical case to 181 trial judges, but some judges also received “expert testimony from a neurobiologist who presented an explanation of the biomechanism contributing to the development of [the] psychopathy”. The results suggested that the inclusion of biomechanical evidence led to significantly reduced sentences for the accused (from 13.93 years to 12.83 years), “and increased the proportion of judges listing mitigating factors (from 29.7 to 47.8%)”. This is an interesting result in light of the growing prevalence of neurolaw. For instance, it demonstrates the need for a discussion on the fundamental differences in a legal context, if any, in formulating the same psychopathy in physiological terms or in psychological terms.

Conclusion

The potential impact and promise of neuroscience in our legal system is unquestionable. Neurolaw could revolutionize the way we think of and apply the law. However, as some of the examples above illustrate, it is important that we tread with caution. The outcomes of many future cases depend on how we answer the many legal and scientific questions raised by the incorporation of neurolaw.

 

[1] Kent Roach, Criminal Law, 4th ed (Toronto: Irwin Law, 2009) at 9.

[2] R v Parks (1990), 73 OR (2d) 129, at paras 14-15.

[3] Ibid at 20.