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What it does 

The Regents of the University of California (“UC”) claimed that The Broad Institute (“Broad”) had patented the same CRISPR-Cas9 technology that they had filed a patent for seven months prior. In January 2016, an interference proceeding was initiated to determine which party first invented the technique. On February 15, 2017, the Patent Trial and Appeal Board ruled that the two claims did not interfere because UC’s CRISPR-Cas9 patent for use in any environment did not “anticipate or render obvious” Broad’s eukaryotic-specific patent. In other words, the court found that, based on UCs patent, the average researcher would not have had a reasonable expectation that the technology would work in eukaryotic cells because UC had only published results in prokaryotic cells and in vitro (a non-cellular environment).

Effects of the Judgment:

  • Because the Court ruled that the parties were patenting sufficiently distinct material, both patents will stand.
  • This ruling sends a message to researchers that small, specific discoveries derived from broader ones can be patented if they are not foreseeable. 
  • The no-interference ruling may create issues in determining who receives CRISPR-Cas9 technology licensing fees. Professor Hank Greely of Stanford Law School predicts that those wishing to use Broad’s patent would also have to license UC’s.
  • Broad had granted Editas Medicine exclusive licensing privileges to develop human gene therapies with their CRISPR technology prior to the decision. Similarly, Caribou Bioscience and Intellia Therapeutics had obtained exclusive licenses from UC, and CRISPR Therapeutics held exclusive licenses for discoveries made by Dr. Emmanuelle Charpentier, a collaborator of UC scientist Dr. Jennifer Doudna. The parties may try to negotiate cross-licensing agreements, a potentially commercially attractive option.
Relevant Science 

CRISPR, short for “clustered regularly interspaced short palindromic repeats,” is a tool that allows scientists to manipulate specific parts of a genome. Although first discovered in 1993 in archaea immune systems, the CRISPR gene editing technique is also naturally used by bacteria to defend against pathogens. Both archaea and bacteria are prokaryotes: simple, single-celled organisms that lack the complex cellular compartmentalization and DNA organization found in eukaryotic cells. Eukaryotes, such as plants and animals, do not naturally have a CRISPR system.

Cas9 is a CRISPR enzyme that cuts double-stranded DNA for the removal, addition, or substitution of a particular DNA sequence. It is led to its target location by guide RNA (gRNA) that binds to a precise section of the DNA strand based on its complementary base pairs. 

In April 2003, researchers announced that they had thus successfully completed the Human Genome Project. With the exact order of base pairs on each chromosome determined, scientists began to map out the functional elements of the genome (primarily genes). Researchers around the world have since contributed their findings to the Encyclopedia of DNA Elements (ENCODE), a public database that has been instrumental in determining the functions and roles of particular genes.

As a result of these continued efforts, we better understand the relationship between genetics and disease. Individuals may be more or less susceptible to certain disorders depending on their particular version or mutation of a gene. For example, BRCA1 and BRCA2 genes normally produce tumor-suppressing proteins, so individuals with inactivating mutations have a higher risk of breast or ovarian cancer. 

Now that CRISPR-Cas9 technology has been adapted to work in human cells, it has immense potential to someday provide in vivo gene therapy by editing problematic DNA sequences.  

Decision Points 

Broad argued that there was no interference-in-fact because its patents were not “anticipate[ed] or render[ed] obvious” by the patents UC had previously filed.

The court found that none of UC’s patents for the CRISPR-Cas9 system were limited to a particular environment, while all of Broad’s were specifically for use in eukaryotic cells.

Broad was able to prove, by a preponderance of the evidence, that the adaptation of CRISPR-Cas9 technology for eukaryotic cells was not rendered obvious by UC’s patents, which were considered the prior art. In determining obviousness, the court asked whether UC’s patents would have suggested “to one of ordinary skill in the art” that Broad’s patents “would have a reasonable likelihood of success.”  Broad argued that “a skilled artisan would not have had a reasonable expectation that the CRISPR-Cas9 system would work successfully in a eukaryotic cell.” The court found this convincing, in part, because it was reasonable to believe that obstacles such as the degradation or toxicity of bacterial RNA and proteins could thwart the adaptation of the technology for use in eukaryotic cells. Furthermore, UC inventors Dr. Jinek and Dr. Doudna’s statements from 2012 indicated that they did not know whether the bacterial system would function in eukaryotic cells.

The facts 

In May 2012, UC filed a patent application for CRISPR-Cas9 technology that could be used in any living cell. This novel genome-editing tool precisely alters specifically targeted DNA sequences and could one day be used to treat or cure genetic diseases in humans. At the time, however, inventors Dr. Jennifer Doudna and Dr. Emmanuelle Charpentier had only demonstrated the technique in prokaryotes and in vitro. In December 2012, Researchers at the Broad Institute filed a patent for CRISPR-Cas9 technology in eukaryotic cells. This patent, and several related ones, were issued in 2014 after fast-track review while UC’s patents remained pending.

In April 2015, UC petitioned the United States Patent and Trademark Office for an interference proceeding to determine who first invented the CRISPR-Cas9 technology. Their request was granted on January 11, 2016, per 37 C.F.R. § 41.202.  

Where & When 

The Patent Trial and Appeal Board of the United States Patent and Trademark Office delivered its ruling on February 15, 2017.

Background 
  • A patent can only be awarded to the first inventor under 35 U.S.C. § 102(g). Thus, when multiple parties contest the right to a patent, the Board of Patent Appeals and Interferences conducts an interference proceeding to determine the rights of each party.
  • Interference proceedings are governed by 35 U.S.C. §135. The Senior Party is the party who filed their patent application first. They are entitled to the presumption that they are the prior inventor. Any other party is a Junior Party.  37 C.F.R. § 41.201 (2015).
  • Courts use a two-way-test to determine if there is an interference-in-fact: “An interference exists if the subject matter of a claim of one party would, if prior art, have anticipated or rendered obvious the subject matter of a claim of the opposing party and vice versa.” 37 C.F.R. § 41.203 (2004). To prevail on its no interference argument, Broad needed to show, by a preponderance of the evidence, that neither of these conditions were met.
Status 

On April 13, 2017, UC issued a statement that it had filed an appeal to overturn the Patent Trial and Appeal Board's decision.

Primary Author 
Kelly Hamachi, JD Candidate
Editor(s) 
Jacqueline Robinson-Hamm, PhD Candidate, Alex Robeson, PhD
Recommended Citation 

Duke SciPol, “The Broad Institute, Inc. v. The Regents of the University of California” available at http://scipol.duke.edu/content/patent-trial-and-appeal-board-rules-dispute-about-crispr-cas9-broad-institute-inc-v-regents (03/20/2017).