Narrower Patent Means CRISPR Victory for Broad Institute

By: Smitha Gundavajhala

On February 28, 2022, the US Patent and Trademark Office (USPTO) handed down a ruling in one of the most bitterly fought patent turf wars in biotechnology: the battle over the use of CRISPR-Cas9 in humans. The two major groups that were vying for recognition were the Broad Institute, consisting of researchers from Harvard, and MIT and CVC, consisting of researchers from UC Berkeley, the University of Vienna, and Emmanuelle Charpentier. 

CRISPR-Cas9 is a revolutionary gene editing tool that has implications for healthcare, agriculture, and more. CRISPRs are DNA sequences with proteins that act like scissors. Originally derived from bacterial genomes, CRISPR technology has since been extended to apply to eukaryotes, which are multicellular organisms. Examples of eukaryotes include plants, animals, and humans. As one might imagine, the latest evolution in CRISPR technology is immensely lucrative. The technology could be used to prevent viral infections and chronic conditions in humans, as well as to genetically modify produce to carry more nutrients.  Both Broad Institute and CVC stood to lose a great deal in their hard-fought dispute about the CRISPR-Cas 9 patent.

The dispute between these parties was complicated by timelines, the change in US patent law, and the contradictory decisions of different jurisdictions across the world. Jennifer Doudna of UC Berkeley was the first to file a patent application in 2012, a few months before Feng Zhang and the Broad Institute filed their patent application. However, prior to 2013, the USPTO’s rules were different: the agency awarded patents to the entity that was the “first to invent,” rather than the entity that was “first to file.” 

Thus, when Doudna asked USPTO to declare an “interference” between the two patents in 2015, the office had to consider which group was the first to invent by “reducing the concept to practice.” CVC argued that Broad Institute’s patent for gene editing in eukaryotes was a mere extension of CVC’s seminal work on CRISPR-Cas9. In 2017, the Patent Trial and Appeal Board (PTAB) ruled that Broad Institute’s patents were not derived from CVC’s patents. In 2019, PTAB again declined to declare an interference regarding claims to CRISPR-Cas9 technology used in eukaryotes, and confirmed that the Broad Institute’s patents were properly issued.

Ultimately, Doudna’s patent application did not explicitly address CRISPR-Cas9 applications for eukaryotes, and Zhang’s patent application did. Thus, Zhang and the Broad Institute were determined to be the “first to invent” CRISPR-Cas9 gene editing for humans. This year’s USPTO decision represents potential losses of billions in licensing revenue for UC Berkeley and priority of invention for Broad Institute.

However, this turf war is far from over and recognition of the Broad Institute’s and CVC’s patents varies across jurisdictions. Currently, CVC maintains fundamental CRISPR-Cas9 patents in over 80 jurisdictions, including China, Japan, and the European Union. CVC and the Broad Institute also face challenges in other countries: South Korea’s ToolGen and Germany’s Sigma Aldrich still have open interference motions with the Broad Institute. From the looks of it, the international fight for CRISPR-Cas9 patent recognition won’t be over any time soon, even while the dust has seemingly settled in the United States.

“Grounded”: Amazon’s Delayed Promise of Aerial Package Delivery

By: Justin Cooper

In late 2013, Amazon CEO Jeff Bezos made a surprise announcement on a segment of 60 Minutes: Amazon was developing small aerial drones capable of delivering packages directly to customers’ doorsteps. He stated that the drones would be used to make speedy thirty-minute deliveries from Amazon fulfillment centers, would have a range of over ten miles, and could carry packages weighing up to five pounds. At that time, he also claimed that the widespread use of drones was at least four to five years away. Nine years later, however, “Amazon Prime Air” is still grounded largely because Amazon’s rollout of delivery drones has faced multiple technical challenges which continue to push back the program’s launch. Although the clearance of FAA regulatory hurdles briefly kindled hope that the program was back on track in 2020, concerns about the privacy and safety of Amazon Prime Air, coupled with the possibility of state and municipal challenges to the program’s rollout, could keep Amazon’s delivery drones grounded well into the future.

During the first few years after Bezos’ announcement, research and development of Amazon Prime Air services seemed to be moving at a steady pace. However, in 2015 the program hit its first snag when the Federal Aviation Administration (FAA), which establishes airworthiness criteria to ensure the safe operation of aircraft in accordance with 49 U.S.C. 44701(a) and 44704, published its widely anticipated rules governing “Unmanned Aerial Systems.” Notably, the FAA refused to green light the use of drones for commercial delivery. Amazon responded with a letter to the FAA “threatening to test the drones abroad if the FAA continued to refuse to let it test the machines outdoors in the United States.” The FAA consequently granted Amazon the ability to conduct limited domestic testing, requiring that drone test flights take place under 400 feet and remain in sight of the pilot and observer. Meanwhile, Amazon continued the development of its drones in the United Kingdom, celebrating its first successful commercial delivery in 2016. Amazon Prime Air’s United Kingdom operation seemed to be advancing even more quickly when “UK regulators…fast-tracked approvals for drone testing.” This fast-tracking “made the country an ideal testbed for drone flights and paved the way for Amazon to gain regulatory approval elsewhere.” However, behind the scenes, Amazon’s program was dealing with major problems, including staff layoffs, redundancies, and reports of mismanagement, including reports of employee drunkenness while on the job

During all of this, and back in the United States, Amazon Prime Air was making slow progress. In 2019, Amazon petitioned the FAA to allow it to begin wide-scale testing of its drones, and a year later the company announced it had received approval from the FAA to begin testing commercial deliveries. Despite this victory, however, Amazon Prime Air has continued to face significant issues that cast doubt on the program’s safety, and an investigative report conducted by Bloomberg News has recently revealed multiple Amazon drone crashes, as well as accounts of a management culture more focused on speed than safety.

This focus on speed likely stems from the fact that Amazon has fallen behind its rivals in the drone delivery space. In August 2021, Alphabet Inc.’s program, Wing, announced that it had successfully made its hundred thousandth delivery in Australia. Wing’s drone deliveries are also automated, “but monitored by pilots who function more as air traffic controllers.” A notable difference from Amazon’s drones is that Wing packages “are dropped in front of homes using a winch”, while Amazon’s drones land to deliver their packages. In addition to Wing, UPS has also successfully tested the use of delivery drones in innovative ways. For example, UPS has tested launching drones from its delivery trucks, which allows a delivery driver to cover large rural areas in a much more efficient manner. 

Aside from the technical and production challenges that have slowed the rollout of Amazon Prime Air, Amazon will likely face continued challenges due to significant privacy concerns. According to CNBC, “detecting telephone wires, people, property and even small animals on the ground all require careful sensing and collision avoidance systems.” In addition to the multiple cameras needed to navigate these obstacles, Amazon “is investing heavily in artificial intelligence to help drones navigate safely to their destinations, and drop off packages safely.” The possibility of fleets of AI-automated drones equipped with precision cameras surveilling American cities, a scene seemingly pulled from a dystopian science fiction novel, could quickly become a concerning reality.

Beyond privacy concerns, Amazon Prime Air will likely have to contend with major safety concerns. Accidents caused by manned drones have already led to multiple legal disputes. For example, in 2017, “[t]he owner of an aerial photography business was sentenced to 30 days in jail and a $500 fine after a drone he was operating crashed into people during a 2015 parade and knocked one woman unconscious. Paul Skinner, 38, was found guilty of reckless endangerment by Judge Willie Gregory of the Seattle Municipal Court.” In the case of piloted drones, victims can bring a suit against the human operator; the widespread use of automated drones, in contrast, raises difficult questions about the increased risk of personal injury and how to apportion blame. Last month, questions about the safety of Amazon’s ground-based “autonomous personal delivery devices”, known as Amazon Scout, led the city of Kirkland, Washington to place a temporary moratorium on their continued use, and as Amazon Prime Air moves towards wide-scale implementation, it could likely face similar slow-downs and push back from various state and local governments. 

Despite these setbacks, Amazon has not faltered in its commitment to implement Amazon Prime Air. The promise of faster, more efficient shipping will very likely continue to outweigh the challenges facing the implementation of aerial delivery drones; this is proven by Amazon’s commitment to launching its program, along with Alphabet Inc.’s and UPS’ already operational delivery drone programs. However, the technical challenges and social concerns surrounding these programs will likely continue to delay their full-scale rollout in the near future, “grounding” Amazon Prime Air for at least a little bit longer.