Patent Trial and Appeal Board rules on a dispute about CRISPR-Cas9 (The Broad Institute, Inc. v. The Regents of the University of California)

The Policy

What it does

Decides that The Regents of the University of California’s and The Broad Institute’s patents on CRISPR-Cas9 technology do not interfere with one another and are thus separately patentable.

Synopsis

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.

Context

<ul>
<li>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.</li>
<li>Interference proceedings are governed by 35 U.S.C. §135. The <em>Senior Party</em> 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 <em>Junior Party</em>. &nbsp;37 C.F.R. § 41.201 (2015).</li>
<li>Courts use a <em>two-way-test</em> to determine if there is an interference-in-fact: “An&nbsp;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.</li>
</ul>

The Science

Science Synopsis

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.  


The Debate