Written By: Aaron Shaw
The genetic engineering tool, CRISPR-Cas9, represents the center of an ongoing patent dispute between the University of California, Berkeley, and the Broad Institute of MIT and Harvard. CRISPR is a protein-based mechanism rendered from bacteria that can be manipulated to precisely splice and replace portions of a plant or animal’s genetic material. [1] Alternative genetic engineering technology are more expensive, taking more time to produce. As a result, CRISPR is a powerful tool that can be put in the hands of many researchers.
High precision genetic engineering will inevitably raise ethical and legal questions about who can receive treatment and for what purpose. Will we limit ourselves to curing genetic diseases or will we allow ourselves to add favorable traits to humans? However, the technology remains in its infancy. [2] The current battle involves the USPTO and EPO as to who owns the patents to CRISPR.
Jennifer Doudna, of the University of California Berkeley, and Emanuelle Charpentier, of the University of Vienna, were the first to discover the potential of CRISPR in prokaryotes (bacteria), and they were the first to apply for a patent. [3] [4] They have encountered fierce opposition from the Broad Institute of MIT and Harvard, who predicate their rights to CRISPR by being the first to examine its use in mammalian cells. [5] [6] The Broad Institute obtained a patent from the USPTO in 2017, for CRISPR’s use in eukaryotes (plant and animal cells). [7] Some would consider this a hard knock to UC Berkeley, since it was the first to publish the genetic engineering potential of the CRISPR mechanism. The obvious next step was to apply the mechanism to eukaryotes. [8]
One month after the Broad Institute received its patent, UC Berkeley was granted a patent for the use of CRISPR in eukaryotes by the EPO. [9] The apparent split decision reveals the complexity of determining the owner of a technology that is groundbreaking, highly lucrative, and used on an international basis. The Europeans stressed that the initial discovery of CRISPR defined the right to use it in a broad field of application. [10] The American approach appears to have narrowed the process, determining that the initial demonstration of CRISPR in a specific setting, such as in animal cells, created the right for its use in animals.
In 2017, one of our law students wrote about the precedent on this blog. [11] At the time, the most recent news was that UC Berkeley and the University of Vienna had defended their right to the broad use of CRISPR in Europe. [12] One reason this appeared to be a never-ending battle involved the rate of CRISPR innovation. Such technologies instigate extended legal battles because scientists cannot discern the parameters. Multiple parties held patents for narrowly defined applications of the CRISPR system. [13] However, the dispute between Berkeley and the Broad Institute still linger as a contentious debate. The EPO’s decision did not seem to resolve the difference between the strategy of using CRISPR in animal cells while defining such use in animal cells.
In 2018, the US Court of Appeals doubled down, confirming there was “‘no interference in fact’” between the two parties’ patents. [14] In July 2019, UC Berkeley claimed the Broad Institute deceived the PTO by withholding information. [15] The Broad Institute believes this is a low blow. [16] Afterall, UC Berkeley has just filed its eleventh patent (and they are expecting six more) involving CRISPR-Cas9; this time the patents involve precise methods and substances for targeting DNA—a vital step for the CRISPR system to modify DNA. [17] Without knowing whether the Broad Institute deceived the PTO, it appears Berkeley has conceded by filing narrow patents in the U.S. It is now clear Berkeley has to compete with all the other discoveries being made, [18][19][20][21] despite not giving up on the dispute. Neither the PTO, nor the EPO, is likely to change patent application requirements any time soon. This feud is likely headed toward a dead end, but neither party can be blamed for their pursuit, given the capital at risk.
This problem underscores the international challenge biotech companies confront. Laboratories and pharmaceutical companies conduct expensive and timely research, [22] subsequently compelled to litigate when parties obtain similar patents in other jurisdictions. This only serves to delay innovation when dealing with such a powerful research tool, and in the case of CRISPR, the issue may go further than the patent offices. The Federal and Drug Administration (FDA) is primarily concerned with somatic cell therapy in humans, but CRISPR-related patent applications are constantly pushing the boundaries of gene editing beyond somatic cell therapy. New technologies advance our understanding of how to apply the law. The FDA and European Medicines Agency must be responsive to new CRISPR products that charter unregulated waters in order to encourage potential innovation.
[1] Jennifer Doudna, Genome-editing revolution: My Whirlwind year with CRISPR, Nature (December 22, 2015), https://www.nature.com/news/genome-editing-revolution-my-whirlwind-year-with-crispr-1.19063 [https://perma.cc/QSV3-Y2JD].
[2] Id.
[3] Heidi Ledford, Why the CRISPR patent verdict isn’t the end of the story, Nature (February 17, 2017), https://www.nature.com/news/why-the-crispr-patent-verdict-isn-t-the-end-of-the-story-1.21510 [https://perma.cc/X4D7-37RC].
[4] Jinek, Marti, et. al., A programmable dual RNA-guided DNA endonuclease in adaptive bacterial immunity, 337 Science 816-821 (2012).
[5] Heidi, supra note 3.
[6] Cong, Le, et. al., Multiplex Genome Engineering Using CRISPR/Cas Systems, 339 Science 819-823 (2013).
[7] Heidi, supra note 3.
[8] Programmable DNA Scissors found for bacterial immune system, Science Daily (June 28, 2012), https://www.sciencedaily.com/releases/2012/06/120628193020.htm [https://perma.cc/72MW-DRCH].
[9] Jef Akst, UC Berkeley Receives CRISPR Patent in Europe, The Scientist (March 24, 2017) https://www.the-scientist.com/?articles.view/articleNo/48987/title/UC-Berkeley-Receives-CRISPR-Patent-in-Europe/ [https://perma.cc/B8WR-3D2B].
[10] Id.
[11] Charles Cheng, A Gene-Editing Patent Dispute – What Does it Mean?, USF Blogs: Intellectual Property and Law Journal (March 28, 2017), https://usfblogs.usfca.edu/iptlj/2017/03/28/a-gene-editing-patent-dispute-what-does-it-mean/#more-1002 [https://perma.cc/ZT9L-K5QL].
[12] Jim Daley, Berkeley CRISPR Inventors Get Another Important European Patent, The Scientist (March 12, 2018), https://www.the-scientist.com/?articles.view/articleNo/52042/title/Berkeley-CRISPR-Inventors-Get-Another-Important-European-Patent/ [https://perma.cc/NTP7-UNMS].
[13] Heidi, supra note 3.
[14] Mark Terry, UC-Berkeley Rekindles U.S. Patent Dispute with the Broad Institute over CRISPR, BioSpace (August 1, 2019), https://www.biospace.com/article/crispr-patent-battle-isn-t-quite-over-yet/ [https://perma.cc/3T9P-4CC3].
[15] Id.
[16] Id.
[17] University of California, U. Vienna, Charpentier Get 11th U.S. CRISPR Cas-9 Patent, ClinicalOmics (August 26, 2019), https://www.clinicalomics.com/topics/precision-medicine-topic/university-of-california-u-vienna-charpentier-get-11th-u-s-crispr-cas-9-patent/ [https://perma.cc/N755-F965].
[18] Jon Cohen, Nirja Desai, With its CRISPR revolution, China becomes a world leader in genome editing, Science (August 2, 2019, 8:00 AM), https://www.sciencemag.org/news/2019/08/its-crispr-revolution-china-becomes-world-leader-genome-editing [https://perma.cc/3N7J-4B3C].
[19] Rich Haridy, CRISPR breakthrough allows scientists to edit multiple genes simultaneously, Newatlas (August 15, 2019), https://newatlas.com/crispr-cas12a-gene-editing-multiple-eth-zurich/61068/ [https://perma.cc/WK2C-A5WW].
[20] CRISPR gene editing may halt progression of triple-negative breast cancer, Medical Xpress (August 26, 2019), https://medicalxpress.com/news/2019-08-crispr-gene-halt-triple-negative-breast.html [https://perma.cc/Z8J3-G4RF].
[21] Hanae Armitage, Scientists Zero in on cancer treatments using CRISPR, Stanford Medicine (August 26, 2019), https://scopeblog.stanford.edu/2019/08/26/scientists-zero-in-on-cancer-treatments-using-crispr/ [https://perma.cc/9WV9-QZT3].
[22] Biotechnology Law, HG.org, https://www.hg.org/biotechnology.html [https://perma.cc/7BNM-H34X] (last visited Jan. 26, 2020).
