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Within the last decade, the genome editor known as CRISPR-Cas9, short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9, has become one of the most exciting and rewarding developments in the scientific community. CRISPR is valued for its ability to create highly specific and targeted edits in DNA sequences, as well as its improved accuracy, efficiency, ease of use, versatility, and cost-effectiveness over previous methods of genome editing. [1]

The CRISPR system, adapted from a naturally occurring immune response employed by bacteria, is akin to a sort of “molecular scissors.” [2] It uses guide sequences of RNA that bind to desired sections of DNA to flag the Cas9 protein to make targeted cuts at those locations in the genome, allowing for new DNA sequences to be added or old ones to be deleted. [3] This incredible technology has broad applications in medicine, agriculture, and research, and there are hopes of harnessing it to treat genetic diseases and disorders, fight hunger with genetically modified crops, and eliminate pathogens. [4]

On October 7th, Emmanuelle Charpentier, at the Max Planck Unit for the Science of Pathogens in Berlin, and Jennifer Doudna, at the University of California, Berkeley, were selected to receive this year’s Nobel Prize in Chemistry for their pioneering work in developing the CRISPR-Cas9 genome editor. [5] Charpentier and Doudna also importantly highlight and celebrate the achievements of women in the sciences, becoming two of only seven women to win the Nobel Prize in Chemistry since its inception in 1901. [6] Their findings were initially published in the landmark Jinek paper in 2012, where they described isolating the components of the CRISPR system and demonstrated the genome editor’s applicability and versatility in laboratory settings. [7] Their work has been largely responsible for a wave of biotechnology companies investing in CRISPR applications, leading to rapid technical developments and a race to commercializiation. [8]

However, the potential commercial rewards have unfortunately sparked a fierce and long-running battle over CRISPR-related patents between Charpentier and Doudna’s group (“UC”) and another research group, The Broad Institute (“Broad”). [9] The Broad team, led by Feng Zhang, published a paper seven months after the Jinek paper which demonstrated the CRISPR system working for eukaryotic cells (i.e., cells found in animals and plants), which the Jinek paper did not. [10]

Both groups have been aggressively pursuing patents for their work but have employed different strategies. The UC group was the first to file its key filings on CRISPR and has attempted to cast a broad net to cover all CRISPR applications. [11] As of October 2019, the UC group holds the largest portfolio of CRISPR patents. [12] However, the Broad group has caught up with the UC group by aggressively pursuing patent prosecution and filing and highlighting the inventiveness of its researchers. [13]

In 2016, at the UC group’s request, an interference was declared by the United States Patent and Trademark Office (USPTO), encompassing the UC group’s key patent application concerning the CRISPR system as discovered in the Jinek paper and 12 of the Broad group’s granted patents and 1 application. [14] An interference proceeding occurs when a patent application’s claims are potentially common to another application or granted patent. [15] Interference proceedings apply only to patents or applications originally filed before 2013, which was the case for both the UC group and the Broad group. [16] The interference proceeding is the method in which the Patent Trial and Appeal Board (PTAB) decides which patent has priority (i.e., which party first invented the commonly claimed invention), which may have ramifications for the patentability of the patent(s) or application(s) which lose the priority contest. [17] In 2017, the PTAB issued a judgment finding no interference-in-fact and thus that both parties’ patents and applications could exist as two separate inventions worthy of patent protection. The PTAB based its decision primarily on the critical issue of obviousness, in that it was not obvious, using a person of ordinary skill in the art (POSA) legal standard, from the UC group’s application for CRISPR in “any environment” that CRISPR would successfully operate in eukaryotic environments as described in the Broad group’s applications and patents. Due to the non-obviousness, the PTAB determined that the two inventions were not common to one another and could both be patentable. [18]

Subsequently, the UC group filed an appeal to the Federal Circuit, arguing that the PTAB had made an erroneous judgment based on incorrect applications of the law. [19] The key issue in the proceedings focused on whether or not the PTAB had sufficient evidence to determine non-obviousness. [20] In September 2018, the Federal Circuit upheld the PTAB’s decision, effectively handing the UC group a defeat over the commercialization of CRISPR applications for eukaryotic cells. [21]

However, the battle continues. Shortly after being denied on appeal, the UC group filed new claims with similar scopes to Broad’s patents that won out the first PTAB holding, triggering a second interference. [22] On September 10, 2020, PTAB granted the Broad group priority within the count. However, their request for a broader count was denied. The “count” in an interference proceeding is the scope of the disputed subject matter and proofs required to win priority. The broader count would have given the Broad group a legal advantage by allowing them to include more patents and applications within the scope of the dispute and gain the usage of some of their earliest proofs of invention which were barred under the existing count. [23] Furthermore, the PTAB ruled that the first interference did not estop the current one. [24]

Though the Broad group has a current advantage in priority, this latest decision leaves the UC group with an advantage on the scope of the priority contest. [25] This uncertainty may create more pressure between the groups to settle, as the interference will now proceed to the priority phase in which both parties will present evidence (e.g., lab notebooks, witnesses, etc.) to determine which was effectively the first to invent. [26] The Broad group’s statement issued on this decision seems to illustrate an openness to settling by noting that “[t]he best thing, for the entire field, is for the parties to reach a resolution and for the field to focus on using CRISPR technology to solve today’s real-world problems.” [27]

This legal battle over the commercialization of CRISPR technologies may have long-term ramifications for advances in genetic engineering. The extensive litigation may make investors and scientists wary of infringing the intellectual property relating to CRISPR, potentially disrupting funding and research going towards life-saving medical and agricultural technologies. [28]

CRISPR’s promise of major beneficial technological advances may even be able to play a significant role in controlling the current COVID-19 pandemic. Various startups and organizations, including the Broad Institute, have been working to develop a CRISPR-based COVID test for use at home that could deliver results in 20 minutes to an hour. [29] As such, it is important that the legal battle concerning the commercialization of CRISPR leads to fair and equitable results that promotes ethical and rapid development of CRISPR technologies in both research and industrial settings.

 

Footnotes

[1] https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/

[2] https://www.sciencemag.org/news/2020/09/latest-round-crispr-patent-battle-has-apparent-victor-fight-continues

[3] Id.

[4] https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/

[5] https://www.nature.com/articles/d41586-020-02765-9

[6] https://www.fastcompany.com/90561762/nobel-prize-jennifer-doudna-emmanuelle-charpentier-crispr-patent-lawsuit

[7] https://science.sciencemag.org/content/337/6096/816.long

[8] https://www.nature.com/articles/d41586-020-02765-9

[9] https://science.sciencemag.org/content/337/6096/816.long

[10] Id.

[11] https://www.allenovery.com/en-gb/global/news-and-insights/crispr/crispr-patent-dispute---us-and-europe#PTAB

[12] https://news.berkeley.edu/2019/10/01/uc-now-holds-largest-crispr-cas9-patent-portfolio/

[13] https://www.sciencemag.org/news/2017/02/how-battle-lines-over-crispr-were-drawn

[14] Id.

[15] https://www.uspto.gov/web/offices/pac/mpep/s2301.html

[16] https://www.allenovery.com/en-gb/global/news-and-insights/crispr/crispr-patent-dispute---us-and-europe#PTAB

[17] https://www.uspto.gov/web/offices/pac/mpep/s2301.html

[18] https://www.allenovery.com/en-gb/global/news-and-insights/crispr/crispr-patent-dispute---us-and-europe#PTAB

[19] Id.

[20] Id.

[21] https://www.nature.com/articles/d41586-018-06656-y

[22] https://www.jdsupra.com/legalnews/patent-trial-and-appeal-board-issues-55160/

[23] Id.

[24] Id.

[25] https://www.sciencemag.org/news/2020/09/latest-round-crispr-patent-battle-has-apparent-victor-fight-continues

[26] Id.

[27] https://www.broadinstitute.org/crispr/journalists-statement-and-background-crispr-patent-process

[28] https://www.fastcompany.com/90561762/nobel-prize-jennifer-doudna-emmanuelle-charpentier-crispr-patent-lawsuit

[29] https://onezero.medium.com/crispr-could-allow-for-fast-at-home-coronavirus-testing-79772fb0d1f8